Lecture 8
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Questions and Answers

What is the role of a mediator in transcription?

  • It binds to the promoter, thus controlling the expression of genes.
  • It acts as a linker, allowing for proper localization of general and specific transcription factors to the promoter. (correct)
  • It is a specific transcription factor that activates or inhibits transcription based on cellular demand for specific proteins.
  • It is a component of the transcription pre-initiation complex which binds to the enhancer or silencer and forms a loop.

What is the primary function of general transcription factors (GTFs)?

  • To bind to the promoter region of a gene and initiate transcription in all cells. (correct)
  • To form a loop between the enhancer/silencer and the promoter, allowing for the regulation of transcription.
  • To bind to specific DNA sequences and activate or repress transcription based on cellular needs.
  • To act as a mediator between the enhancer/silencer and the promoter, facilitating the interaction of specific transcription factors with the promoter.

What is the main difference between general transcription factors (GTFs) and specific transcription factors (STFs)?

  • GTFs are protein complexes, while STFs are single proteins
  • GTFs bind to the promoter, while STFs bind to the enhancer or silencer.
  • GTFs are involved in the initiation of transcription, while STFs are involved in the elongation of the transcript.
  • GTFs are always active and involved in basal transcription, while STFs are activated based on specific cellular demands. (correct)

What is the purpose of the loop formed between the enhancer/silencer and the promoter?

<p>To create a physical connection between the enhancer/silencer and the promoter, allowing for regulation of transcription. (C)</p> Signup and view all the answers

Which of the following are true about transcription regulators? (Select all that apply)

<p>They bind to DNA regulatory sequences. (A), They are essential for the combinatorial control of gene expression. (C), They act as switches that regulate transcription. (D)</p> Signup and view all the answers

How do transcription regulators recognize specific DNA sequences?

<p>By recognizing specific base pairs in the major groove of DNA. (A)</p> Signup and view all the answers

What is the structural motif called that is formed by transcription regulators with at least three α helices that fit into the major groove of DNA?

<p>Homeodomain (C)</p> Signup and view all the answers

What is the significance of dimerization in transcription regulators?

<p>It increases the contact area between the transcription regulator and DNA, strengthening the interaction. (B)</p> Signup and view all the answers

What is combinatorial control in gene expression?

<p>The coordinated action of multiple transcription regulators working together to determine the expression of a specific gene. (B)</p> Signup and view all the answers

Which of the following statements about trans regulatory sequences are true? (Select all that apply)

<p>They function to act as switch regulating transcription. (A), They encode transcription factors. (C), They can involve protein-protein interactions. (D)</p> Signup and view all the answers

What is the primary function of a gene in eukaryotic cells?

<p>To code for a sequence of nucleotides in mRNA (D)</p> Signup and view all the answers

What percentage of DNA in humans consists of protein-coding genes?

<p>1.5% (A)</p> Signup and view all the answers

Which statement about housekeeping proteins is true?

<p>They include proteins that are essential for basic cellular functions. (C)</p> Signup and view all the answers

What is the key regulatory step for most genes during gene expression?

<p>Transcription (D)</p> Signup and view all the answers

Which of the following is a characteristic of cis-regulatory sequences?

<p>They influence the gene they are located next to. (A)</p> Signup and view all the answers

What role do transcription regulators play in gene expression?

<p>They act as switches to regulate transcription. (B)</p> Signup and view all the answers

Which type of regulatory sequence typically acts over long distances?

<p>Silencers and enhancers (D)</p> Signup and view all the answers

How can eukaryotic cells regulate their protein synthesis?

<p>By controlling transcription and degradation of mRNA. (D)</p> Signup and view all the answers

Which type of RNA is encoded by a gene that produces a polypeptide?

<p>mRNA (C)</p> Signup and view all the answers

What characterizes the differentiated cells in a multicellular organism?

<p>They can express a variable number of genes depending on their function. (A)</p> Signup and view all the answers

What distinguishes trans-acting regulatory elements from cis-regulatory elements?

<p>Trans elements can act on different chromosomes. (C)</p> Signup and view all the answers

Which mechanism primarily facilitates the transport of mRNA from the nucleus to the cytoplasm?

<p>Nuclear pore complex (A)</p> Signup and view all the answers

Which gene expression regulation involves proteins that inhibit transcription?

<p>Transcription repressors (A)</p> Signup and view all the answers

What is the relationship between the structural differences of tissues and gene expression?

<p>Different genes are expressed in different tissues, resulting in functional variations. (A)</p> Signup and view all the answers

What is the main difference between euchromatin and heterochromatin?

<p>Euchromatin is less tightly packed than heterochromatin. (A)</p> Signup and view all the answers

Which of the following is NOT a common histone modification?

<p>Glycosylation (B)</p> Signup and view all the answers

Which of the following is NOT a function of DNA methylation?

<p>Replicating DNA (C)</p> Signup and view all the answers

What is the role of methyl-CpG binding domain (MBD) proteins?

<p>Recognizing and binding to methylated CpG sequences in DNA. (A)</p> Signup and view all the answers

What is the significance of the CpG dinucleotide in DNA methylation?

<p>It is the most common site for methylation in vertebrates. (A)</p> Signup and view all the answers

What is the role of histone acetyltransferases (HATs) in chromatin remodeling?

<p>HATs add acetyl groups to histone tails, leading to gene activation. (C)</p> Signup and view all the answers

What is the role of histone deacetylases (HDACs) in chromatin remodeling?

<p>HDACs remove acetyl groups from histone tails, leading to gene silencing. (C)</p> Signup and view all the answers

What is the main mechanism of "histone octamer shift" in chromatin remodeling?

<p>The histone octamer slides along the DNA strand. (A)</p> Signup and view all the answers

What is the role of RNA interference (RNAi) in epigenetic regulation?

<p>RNAi can indirectly affect DNA methylation and histone modifications, leading to gene silencing. (B)</p> Signup and view all the answers

How do epigenetic patterns change during development?

<p>Epigenetic patterns are erased and re-established at various stages of development. (D)</p> Signup and view all the answers

Which of the following is an example of epigenetic regulation contributing to cellular identity?

<p>The difference in gene expression patterns between a muscle cell and a nerve cell. (A)</p> Signup and view all the answers

What is the main function of the "barrier sequences" that are mentioned in the context of chromatin remodeling?

<p>Barrier sequences block the spread of heterochromatin formation, preventing gene silencing. (C)</p> Signup and view all the answers

Which of the following statements about histone modification during DNA replication is TRUE?

<p>Newly synthesized DNA receives a mixture of modified and unmodified histones, with the patterns influenced by the parent strand. (D)</p> Signup and view all the answers

What is the main difference between "chromatin remodeling" and "histone modification"?

<p>Chromatin remodeling involves altering the structure of the nucleosome, while histone modification involves altering the chemical composition of histone proteins. (B)</p> Signup and view all the answers

Which of the following is NOT a typical participant in chromatin remodeling?

<p>RNA polymerase (D)</p> Signup and view all the answers

What is the main outcome of the epigenetic reprogramming cycle during gametogenesis and early embryogenesis?

<p>The selective erasure of some epigenetic patterns and the establishment of new patterns, specific to germline or somatic cells. (C)</p> Signup and view all the answers

What is the role of multiple transcription regulators in eukaryotes?

<p>They help in the coordination of mediator assembly and transcription factors. (B)</p> Signup and view all the answers

What occurs as a result of alternative promoter usage?

<p>Different transcripts and proteins from the same gene depending on the tissue. (D)</p> Signup and view all the answers

How does alternative splicing contribute to protein diversity?

<p>By producing different combinations of exons. (B)</p> Signup and view all the answers

Which statement about poly(A) sites is true?

<p>Use of different poly(A) sites can lead to variations in mRNA stability and location. (B)</p> Signup and view all the answers

What is the primary function of the RISC complex formed by miRNA?

<p>To degrade target mRNA or inhibit its translation. (C)</p> Signup and view all the answers

In what context does RNA editing alter gene expression?

<p>By inserting or deleting nucleotides in the mRNA sequence. (B)</p> Signup and view all the answers

What distinguishes lncRNAs from other types of RNA?

<p>They play significant regulatory roles in gene expression. (B)</p> Signup and view all the answers

Which of the following describes the characteristic of heterochromatin?

<p>It is tightly packed and transcriptionally inactive. (B)</p> Signup and view all the answers

What is the primary outcome of the action of small interfering RNA (siRNA)?

<p>Degrading target mRNA to inhibit its production. (D)</p> Signup and view all the answers

What mechanism allows a single pre-mRNA molecule to produce multiple protein forms?

<p>Alternative polyadenylation. (C)</p> Signup and view all the answers

What is an example of the effects of transcriptional regulators during embryonic development?

<p>They contribute to the differentiation of various cell types. (C)</p> Signup and view all the answers

What role do transcription factors play in the process of gene expression?

<p>They assist in the binding of RNA polymerase to DNA. (B)</p> Signup and view all the answers

Which of the following correctly describes gene expression regulation via epigenetic mechanisms?

<p>It can be modified by external factors without changing the DNA sequence. (A)</p> Signup and view all the answers

How does the use of specific RNA editing in liver and intestinal cells affect ApoB protein synthesis?

<p>Liver cells produce a longer ApoB while intestinal cells produce a shorter one. (B)</p> Signup and view all the answers

What role does the mediator protein play in transcription?

<p>It connects transcription factors to the transcription pre-initiation complex. (D)</p> Signup and view all the answers

Which statement about general transcription factors (GTFs) is true?

<p>GTFs are the same across different types of eukaryotic genes. (D)</p> Signup and view all the answers

What defines a transcription regulator's ability to recognize DNA sequences?

<p>It relies on the precise fitting of the protein’s surface to the DNA structure. (D)</p> Signup and view all the answers

Which of the following statements about combinatorial control is accurate?

<p>Multiple transcription factors work together to express genes under specific conditions. (A)</p> Signup and view all the answers

How do specific transcription factors (STFs) differ from general transcription factors (GTFs)?

<p>STFs can be activated or inhibited based on cellular needs, unlike GTFs. (B)</p> Signup and view all the answers

What type of interaction do transcription regulators primarily use to bind to DNA?

<p>Hydrogen bonds, ionic bonds, and hydrophobic interactions through dimerization. (C)</p> Signup and view all the answers

In the context of transcription regulation, what is the function of trans regulatory sequences?

<p>They encode transcription factors that work through DNA-protein and protein-protein interactions. (C)</p> Signup and view all the answers

What is the significance of the major groove in DNA for transcription regulators?

<p>It is the site where transcription regulators form specific connections with base pairs. (C)</p> Signup and view all the answers

Why is dimerization of regulatory proteins important in transcription regulation?

<p>It increases the binding specificity and interaction area with DNA. (A)</p> Signup and view all the answers

Which type of bond is least likely to be formed between transcription regulators and DNA?

<p>Covalent bonds (B)</p> Signup and view all the answers

What is a primary consequence of DNA methylation on gene expression?

<p>Blocks gene transcription (D)</p> Signup and view all the answers

In the context of X chromosome inactivation, what is the role of DNA methylation?

<p>Prevents transcription of genes on one X chromosome (D)</p> Signup and view all the answers

What characterizes the inheritance of DNA methylation patterns during cell division?

<p>One strand is inherited as methylated and the other as unmethylated (B)</p> Signup and view all the answers

Which of the following histone modifications is associated with decreased gene expression?

<p>H3 K9 methylation (B)</p> Signup and view all the answers

Which mechanism allows for the modification of newly synthesized histones during DNA replication?

<p>Proteins binding to previous modified histones (D)</p> Signup and view all the answers

What is the primary action of histone acetyltransferases (HATs) in chromatin remodeling?

<p>To add acetyl groups to histone tails, increasing transcription (D)</p> Signup and view all the answers

What effect does histone deacetylation have on chromatin structure?

<p>Condenses chromatin and inhibits transcription (C)</p> Signup and view all the answers

Which type of modification is NOT a common histone modification?

<p>Glycosylation (B)</p> Signup and view all the answers

Which of the following describes a function of RNA interference (RNAi)?

<p>Regulates transcription through methylation and histone modifications (C)</p> Signup and view all the answers

How does histone methylation contribute to chromatin remodeling?

<p>By promoting either euchromatin or heterochromatin formation (D)</p> Signup and view all the answers

What is the initial mechanism of chromatin remodeling involving the histone octamer?

<p>Loosening of nucleosomal DNA via ATP hydrolysis (C)</p> Signup and view all the answers

In the process of chromatin remodeling, what do barrier sequences help prevent?

<p>Further spreading of heterochromatin formation (A)</p> Signup and view all the answers

What common function do histone modifications serve in transcription regulation?

<p>Induce structural changes in chromatin accessibility (B)</p> Signup and view all the answers

What is a critical feature of histone tails that allows for modification?

<p>They extend beyond the nucleosome's globular structure (A)</p> Signup and view all the answers

What best describes the functional difference between housekeeping proteins and specialized proteins in differentiated cells?

<p>Housekeeping proteins facilitate basic metabolic functions, while specialized proteins are involved in specific roles. (D)</p> Signup and view all the answers

Which statement accurately characterizes eukaryotic gene expression?

<p>Transcription occurs independently of translation in eukaryotes. (D)</p> Signup and view all the answers

How do long-range cis-regulatory sequences function in gene expression regulation?

<p>They can influence transcription regardless of their orientation relative to the promoter. (A)</p> Signup and view all the answers

What role do transcription regulators play in cis-regulatory sequences?

<p>They must recognize specific DNA sequences to effectively regulate transcription. (A)</p> Signup and view all the answers

What is a primary mechanism by which differentiated cells can change their gene expression patterns?

<p>By responding to both intracellular and extracellular signals. (D)</p> Signup and view all the answers

What defines the significance of enhancers and silencers in gene transcription?

<p>They can function independently of their distance to the promoter. (B)</p> Signup and view all the answers

Which of the following is true about the transcription factors associated with cis-regulatory sequences?

<p>They can interact with DNA at regulatory sequences to modulate gene expression. (A)</p> Signup and view all the answers

What primarily characterizes the process of alternative splicing in gene expression?

<p>It alters the final protein product by generating different combinations of exons. (D)</p> Signup and view all the answers

Why is the organization of genes and regulatory elements significant in eukaryotic cells?

<p>It allows for the specific activation of genes required in particular cell types. (D)</p> Signup and view all the answers

What would be an incorrect assumption about the encoding capability of eukaryotic genes?

<p>The majority of a eukaryotic genome is made up of protein-coding regions. (C)</p> Signup and view all the answers

What is the primary reason for the variability of protein expression levels in different cell types?

<p>Different cells have unique sets of regulatory proteins that control gene transcription. (A)</p> Signup and view all the answers

In the context of gene expression regulation, what is a critical factor affecting mRNA degradation?

<p>The specific regulatory proteins that bind to the mRNA. (C)</p> Signup and view all the answers

Which of the following is a misconception about the role of non-coding DNA in eukaryotes?

<p>Non-coding DNA has no regulatory function. (C)</p> Signup and view all the answers

What is the primary advantage of combinatorial control in gene regulation during embryonic development?

<p>It ensures that multiple genes can be regulated simultaneously with fewer regulators. (C)</p> Signup and view all the answers

Which mechanism allows a gene to produce different mRNA transcripts in different tissues?

<p>Alternative promoters (C)</p> Signup and view all the answers

How does alternative splicing contribute to the generation of protein diversity?

<p>By altering exon arrangements and resulting in different protein variants. (C)</p> Signup and view all the answers

What is one consequence of using different poly(A) sites in gene expression?

<p>Formation of mRNA with varying lengths and stability. (A)</p> Signup and view all the answers

Which of the following best describes the role of regulatory RNAs, such as miRNA?

<p>They mediate RNA degradation or inhibit translation. (B)</p> Signup and view all the answers

What is the primary function of the RITS complex in relation to RNA interference?

<p>To inhibit transcription of complementary sequences. (B)</p> Signup and view all the answers

In the context of RNA editing, which type of change primarily occurs in mammals?

<p>Changes of cytosine to uridine. (C)</p> Signup and view all the answers

What condition leads to the synthesis of two forms of apolipoprotein B in different tissues?

<p>RNA editing resulting in different mRNA forms. (C)</p> Signup and view all the answers

Which aspect of chromatin structure is affected by epigenetic mechanisms?

<p>The degree of condensation of chromatin. (C)</p> Signup and view all the answers

Which statement about long non-coding RNAs (lncRNAs) is true?

<p>lncRNAs can influence chromatin structure and gene expression. (B)</p> Signup and view all the answers

What is primarily monitored during the decision-making process after each cell division in embryonic development?

<p>The synthesis of regulatory proteins. (D)</p> Signup and view all the answers

What distinguishes the action of alternative promoters from alternative splicing in gene expression control?

<p>Alternative promoters affect transcription in a tissue-specific manner. (D)</p> Signup and view all the answers

Why is the concept of epigenetics important in understanding gene expression changes?

<p>It accounts for inheritable expression changes not involving DNA sequence alterations. (D)</p> Signup and view all the answers

In humans, what is the impact of glucocorticoid hormones like cortisol on gene regulation?

<p>They coordinate the expression of multiple genes through shared regulatory sequences. (B)</p> Signup and view all the answers

Flashcards

Gene expression

The process by which cells synthesize proteins and RNA molecules based on the instructions in their DNA.

Transcription regulators

Specialized proteins that regulate gene expression by binding to regulatory DNA sequences.

Regulatory sequences

DNA sequences that control when and how much a gene is transcribed.

Promoters

DNA sequences located upstream of a gene that promote transcription initiation.

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Enhancers

DNA sequences that can be located far away from the gene and enhance transcription.

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Silencers

DNA sequences that can inhibit transcription.

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Cis-regulatory sequences

Regulatory sequences that are located on the same chromosome as the gene they regulate.

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Trans-regulatory sequences

Regulatory sequences that are located on a different chromosome than the gene they regulate.

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Short-range cis-regulatory sequences

Cis-regulatory sequences located close to the start of a gene, often within the promoter region.

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Long-range cis-regulatory sequences

Cis-regulatory sequences located far away from the start of a gene.

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Activators

Regulatory sequences that enhance the rate of transcription.

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Repressors

Regulatory sequences that decrease the rate of transcription.

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Transcription

The process by which a gene is transcribed into RNA.

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Translation

The process by which an RNA molecule containing the genetic code is translated into protein.

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Gene

A single unit of DNA that carries instructions for building one polypeptide or functional RNA.

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Enhancer/Silencer

DNA sequence that can bind regulatory proteins and influence gene expression. They can be located far from the gene they regulate.

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Spacer DNA

The DNA between an enhancer/silencer and a promoter, which forms a loop to bring the regulatory protein closer to the promoter.

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Mediator

A protein complex that connects enhancers/silencers to the promoter, allowing for long-distance regulation.

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Transcription Factors

Proteins that bind to DNA and control gene expression by activating or repressing transcription.

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General Transcription Factors (GTFs)

Required for all genes transcribed by RNA polymerases, they ensure the basic process of transcription.

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Specific Transcription Factors (STFs)

Activated or inhibited based on the cell's specific needs, they control the expression of specific genes.

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Combinatorial Control

The way in which multiple transcription factors work together to regulate gene expression.

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Coordinated Gene Regulation

A single transcription factor can regulate the expression of multiple genes, ensuring coordinated activation or deactivation.

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Shared Regulatory Sequences

Different genes can share the same regulatory sequences, allowing a single transcription factor to control their expression simultaneously.

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Cell Differentiation

The process by which cells become specialized with unique functions and characteristics.

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Transcriptional Control

The regulation of gene expression at the level of transcription, including the use of alternative promoters.

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Alternative Promoters

Different starting points for transcription within a gene, allowing for tissue-specific gene expression.

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Alternative Splicing

A process that creates different mature mRNA transcripts from a single pre-mRNA by selectively splicing out or including exons.

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Poly(A) Sites

Locations on pre-mRNA where cleavage and polyadenylation occur, determining the length and stability of the final mRNA.

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RNA Editing

A molecular mechanism where the sequence of a primary transcript is altered by the insertion, deletion, or modification of nucleotides.

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Regulatory RNA

A class of non-coding RNAs that play a significant role in regulating gene expression.

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MicroRNA (miRNA)

Small non-coding RNA molecules that regulate gene expression by binding to target mRNAs, leading to translational repression or mRNA degradation.

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Small Interfering RNA (siRNA)

Small non-coding RNA molecules involved in RNA interference (RNAi), which can silence genes by destroying target mRNAs.

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Long Non-coding RNA (lncRNA)

Long non-coding RNA molecules that can regulate gene expression through various mechanisms, including chromatin remodeling and transcription regulation.

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Epigenetics

The study of heritable changes in gene expression that occur without alterations in DNA sequence.

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Chromatin Structure

The packaging of DNA with proteins to form chromatin, which can be condensed to varying degrees, affecting gene expression.

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What is epigenetic regulation?

Epigenetic regulation is the process of changing chromatin structure without altering the DNA sequence. It affects gene expression by influencing how tightly or loosely DNA is packed.

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What is DNA methylation?

DNA methylation is the addition of a methyl group to a cytosine base in DNA. This can alter gene expression by promoting chromatin condensation and blocking transcription.

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Where does methylation usually happen?

The sequence 5’-CG-3’ (CpG) is where methylation often occurs in vertebrates. The 'C' in this sequence is the cytosine that gets methylated.

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What are MBD proteins and what do they do?

Methyl-CpG Binding Domain (MBD) proteins recognize and bind to methylated cytosines in DNA, playing a role in gene regulation.

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How does methylation impact gene expression?

Methylation of cytosine in DNA can lead to a tighter packing of chromatin, making the genes in that region harder to access and thus inhibiting their transcription.

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What are some significant roles of DNA methylation?

DNA methylation is essential for cell identity, X chromosome inactivation, gene reprogramming, and genetic imprinting.

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How are methylation patterns inherited?

DNA methylation patterns are copied during cell division, ensuring that each daughter cell inherits the methylation pattern of the parent cell.

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What is X chromosome inactivation and why is it important?

In female mammals, one X chromosome is inactivated by methylation, ensuring equal expression of X-linked genes between males and females.

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What are histone proteins and what is their structure?

Histone proteins are involved in packaging DNA into nucleosomes, which are the basic building blocks of chromatin. They have both a globular part and a tail.

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What are histone modifications? How do they happen?

Histone modifications are reversible changes to histone tails that affect DNA accessibility and gene transcription. Common modifications include phosphorylation, acetylation, and methylation.

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How does acetylation affect chromatin and gene expression?

Histone acetylation loosens chromatin, making genes more accessible and increasing transcription. Conversely, deacetylation tightens chromatin, inhibiting gene expression.

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How does methylation of lysine residues affect gene expression?

Methylation of specific lysine residues on histone tails can either promote euchromatin formation and increased gene expression or heterochromatin formation and reduced gene expression, depending on the location of the methylation.

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How are histone modifications inherited during DNA replication?

During DNA replication, histones are distributed to daughter chromosomes, with some inherited modifications and some new modifications added by proteins that recognize modified histones.

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What is chromatin remodeling?

Chromatin remodeling involves changing chromatin structure to control gene expression. It involves the action of histone-modifying enzymes and chromatin-remodeling complexes.

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What is one mechanism of chromatin remodeling?

Chromatin remodeling complexes can shift histone octamers along the DNA strand, using ATP hydrolysis for energy. This exposes DNA sequences, making them more accessible for transcription.

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Housekeeping genes

A set of genes that are constantly expressed in most cells to maintain basic cellular functions.

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Epigenetic regulation

The process of changing chromatin structure without altering the DNA sequence, affecting gene expression.

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DNA methylation

The addition of a methyl group to a cytosine base in DNA.

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MBD proteins

Proteins that recognize and bind to methylated cytosines in DNA, contributing to gene regulation.

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Histone modifications

Reversible changes to histone tails that affect DNA accessibility and gene transcription.

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DNA-protein interactions

The process by which regulatory proteins bind to DNA sequences, forming non-covalent bonds with nucleotides within the major groove of DNA.

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Homeodomain

A structural motif found in regulatory proteins, usually involving three α helices that fit into the major groove of DNA and form base pair connections.

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Dimerization

When two regulatory proteins bind together to increase the contact area and affinity of the DNA-protein interaction. This strengthens the bond and improves regulation.

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Dimerization of regulatory proteins

Regulatory proteins often bind to DNA as dimers, where two protein molecules associate to increase the contact area and strength of the DNA-protein interaction.

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Alternative poly(A) sites

Creating different versions of mature mRNA transcripts by cleaving at different poly(A) sites, like a ruler with multiple markings to measure different lengths.

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miRNA (microRNA)

Small non-coding RNA molecules that regulate gene expression by binding to target mRNAs, leading to the degradation of mRNA or a block in translation, like a security guard preventing unwanted entry into a building.

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siRNA (small interfering RNA)

Small non-coding RNA molecules involved in RNA interference (RNAi), which can silence genes by destroying target mRNAs, like a trash collector removing unwanted garbage from a city.

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lncRNA (long non-coding RNA)

Long non-coding RNA molecules that can regulate gene expression through various mechanisms, like a master conductor orchestrating a complex symphony within the cell.

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Chromatin remodeling

A process that changes chromatin structure to control gene expression by using histone-modifying enzymes and chromatin-remodeling complexes, like a mechanic adjusting the engine of a car to improve its performance.

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What are MBD proteins?

MBD (Methyl-CpG Binding Domain) proteins are a family of proteins that recognize and bind to methylated cytosines in DNA, playing a role in gene silencing.

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What is X chromosome inactivation?

X chromosome inactivation is an epigenetic process where one of the two female X chromosomes is silenced by methylation in each cell. This ensures equal X-linked gene expression in females and males.

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What are histone proteins and their structure?

Histone proteins are involved in packaging DNA into nucleosomes, the basic building blocks of chromatin. Histone tails extend beyond the nucleosome and are subject to various modifications.

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What are histone modifications?

Histone modifications are reversible changes to histone tails, including acetylation, methylation, and phosphorylation. These modifications influence chromatin structure and gene expression.

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How does histone acetylation affect gene expression?

Histone acetylation involves the addition of acetyl groups to lysine residues in histone tails, typically loosening chromatin and increasing gene expression.

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How does histone methylation affect gene expression?

Histone methylation involves the addition of methyl groups to lysine or arginine residues in histone tails. Depending on the location and type of methylation, it can promote either euchromatin formation (activation) or heterochromatin formation (silencing).

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How are histone modifications inherited?

During DNA replication, histones are distributed to daughter chromosomes, with some inherited modifications and some new modifications added by proteins that recognize modified histones. This ensures a degree of epigenetic inheritance.

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How can the histone octamer be shifted?

One mechanism of chromatin remodeling involves shifting the histone octamer along the DNA strand by ATP-dependent chromatin remodeling complexes. This can expose DNA sequences, making them more accessible for transcription.

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How can non-coding RNAs affect epigenetic regulation?

Non-coding RNAs, such as microRNAs (miRNAs), can regulate gene expression through epigenetic mechanisms involving DNA methylation, histone modification, and chromatin remodeling.

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How can the environment affect epigenetic regulation?

Epigenetic changes can be influenced by environmental factors, such as diet, stress, and exposure to toxins. These changes can affect health and disease, highlighting the importance of a holistic approach to understanding health.

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What is epigenetic reprogramming?

Epigenetic reprogramming is a crucial process during development where methylation patterns are erased and re-established in a specific manner, contributing to cell differentiation and the proper development of tissues.

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Study Notes

Control of Gene Expression

  • Lecturer: Dr. Michelle Kuzma
  • Adapted from: Dr. Danuta MielżyÅ„ska-Å vach
  • Book reference: Essential Cell Biology, 6th Edition by Bruce Alberts
  • Focus on content discussed in lectures
  • Chapters: 8 (Control of Gene Expression), 9 (How Genes and Genomes Evolve)

Gene Expression in Eukaryotes

  • Cells in multicellular organisms became interdependent, sacrificing individual independence for the common good
  • Multicellular organism activities resemble a large metropolis
  • Prokaryotic cells resemble a small cottage in the middle of nowhere

Human Genome

  • Nuclear genome: 3000 Mb, 30,000 genes
  • Mitochondrial genome: 16.6 kb, 37 genes
  • Coding DNA: 10%
  • Non-coding DNA: 90%
  • Genes and gene-related sequences: 30%
  • Extragenic DNA: 70%
  • Two rRNA genes: 80%
  • 22 tRNA genes:
  • 13 polypeptide-encoding genes: 20%
  • Pseudogenes, gene fragments, introns, untranslated sequences, etc.
  • Unique or low copy number
  • Tandemly repeated or clustered repeats
  • Moderate to highly repetitive interspersed repeats

Eukaryotic Gene

  • A gene is a fragment of DNA that encodes a product
  • A gene carries information for polypeptide structure (mRNA)
  • A gene carries information for functional non-coding RNA (e.g., rRNA, tRNA, snRNA, miRNA)

Eukaryotic Gene Sequences

  • Coding sequences (exons)
  • Non-coding sequences (introns)
  • Regulatory sequences
  • Promoter
  • Enhancers
  • Silencers

Eukaryotic Gene Structure

  • DNA 5' --> 3'
  • Upstream regulatory sequence
  • Distal control elements
  • Proximal control elements
  • Open reading frame (ORF)
  • Downstream regulatory sequence
  • Intron
  • Poly-A signal sequence
  • Exon
  • Promoter (TATA box)
  • Enhancer/Silencer
  • Terminator

Gene Expression in Eukaryotes

  • Genetic material of somatic cells is identical
  • Differentiated human cell expresses 5,000-1,000 genes out of 25,000 protein-coding genes
  • Protein-coding genes represent 1.5% of DNA, while 98.5% is non-protein-coding.
  • Gene expression is the process where cells synthesize proteins and RNA from their DNA.
  • In each differentiated cell type, the set of expressed genes remains constant.
  • Cells can alter gene expression patterns in reaction to intracellular and extracellular signals

Expression of Genes in Eukaryotes

  • In somatic cells, most proteins are the same.
  • Called "housekeeping proteins" and include:
    • DNA and RNA polymerases
    • DNA repair enzymes
    • Ribosomal proteins
    • Enzymes associated with basic metabolic processes

Gene Expression in Eukaryotes - Examples

  • Pancreatic ß-cells produce insulin
  • Pancreatic α-cells produce glucagon
  • B cells (lymphocytes) produce antibodies
  • Red blood cells synthesize hemoglobin

Gene Expression in Eukaryotes - Steps

  • DNA --> RNA transcript (transcriptional control)
  • RNA processing (RNA processing control)
  • mRNA transport and localization (mRNA transport and control)
  • mRNA translation (translation control)
  • protein activity, degradation
  • mRNA degradation (mRNA degradation control)

Gene Expression Regulation

  • Cells regulate protein sets by
    • Controlling when and how often a given gene is transcribed
    • Controlling transcript maturation steps
    • Selectively exporting mRNAs to cytoplasm.
    • Regulating mRNA degradation speed
    • Selecting mRNAs for ribosome translation
    • Regulating protein degradation rate

Types of Expression Regulation

  • Key regulatory step, largely: transcription
  • Transcription begins when RNA polymerase and transcription factors bind to the gene promoter.
  • Most genes have additional DNA regulatory sequences for transcription control

Types of Regulatory Sequences

  • Cis-type: on the same chromosome as the regulated gene
  • Trans-type: on a different chromosome

Cis-Regulatory Sequences

  • Divided into short-range and long-range sequences
  • Short-range: promoters, enhancers, and silencers in the 5' UTR region Long-range sequences act over larger distances

DNA Regulatory Sequences

  • Regulators do not function independently.
  • Recognition by a transcription regulator protein turns them on or off

Models for Action "at a Distance"

  • Activator or repressor protein binds to enhancer or silencer sequences far from promoter
  • DNA loops connect enhancer (silencer) and promoter to let the regulator protein contact transcriptional pre-initiation complex
  • Mediators act as linkers for correct localization of general or specific transcription factors to the promoter region with RNA polymerase.

Transcription Factors

  • GTFs (general transcription factors) remain active throughout the cell's lifetime
  • STFs (specific transcription factors) are activated/inhibited in response to cell requirements for specific proteins

General transcription factors associated with a promoter are the same for all genes transcribed by RNA polymerase.

Specific transcription factors and DNA-binding sites vary between genes.

Combinatorial control

  • Most eukaryotic transcription regulators cooperate in complex systems
  • The combination of proteins determines expression of specific genes

In Eukaryotes, expression generally is controlled by multiple factors together

Types of Expression Regulation (continued):

  • Promoter is first regulatory sequence where RNA polymerase and transcription factors bind

Cis-regulatory sequences

  • Short-range regulatory sequences, like promoters, enhancers, and silencers influence nearby genes
  • Long-range sequences act over larger distances

Regulatory Sequences (continued)

  • Binding by transcription regulators acts as a switch

Regulatory Trans Sequences

  • They are sequences that encode transcription factors that influence other genes via interactions (DNA-protein, protein-protein, RNA-protein)

Transcription Regulators

  • Transcription regulator proteins recognize DNA regulatory sequences
  • Their binding acts as a switch that regulates transcription

Transcription Regulators (continued)

  • They are proteins whose surfaces tightly fit DNA surfaces
  • Noncovalent bonds with nucleotides in the major groove of DNA
  • Interactions may also occur in the minor groove with bases
  • Strong and specific DNA/protein interactions
  • Use at least three a helices, fitting into DNA major groove and connecting with base pairs
  • Asparagine side chain of third helix forms hydrogen bonds with adenine bound to thymine

Transcription Regulators (continued)

  • DNA-protein interface contains 10-20 interactions, involving varying amino acids
  • Interactions include hydrogen, ionic, hydrophobic bonds

Dimerization

  • Protein dimers increase the surface area for DNA-protein interaction

Chromatin Remodeling

  • Remodeling alters chromatin structure (condensation/loosening) by histone-modifying enzymes and chromatin-remodeling complexes

Chromatin Remodeling (continued)

  • Some gene activators/repressors recruit proteins to promoters by:
  • Histone acetyltransferase — adds acetyl groups, increasing gene transcription
  • Histone deacetylase — removes acetyl groups, reducing gene transcription

Chromatin Remodeling (continued)

  • Modifications create waves
  • Barrier sequences prevent heterochromatin spread.

Histone Octamer Shift

  • A chromatin remodeling mechanism that moves histone octamers to alter DNA access.
  • Protein complexes use energy ATP hydrolysis to loosen nucleosomal DNA and push it out of the nucleosome, making it accessible to enable transcription.

RNA Interference (RNAi)

  • A defense mechanism against viruses present in eukaryotes.
  • Some RNAi inhibit transcription of specific genes via DNA modifications, RNAi-dependent DNA methylation, and histone protein modifications.

Epigenetics

  • The study of changes to gene expression without altering the DNA sequence
  • Epigenetic mechanisms include inheritance and modification by external factors.

Epigenetic Regulation

  • DNA with proteins create chromatin that can be condensed to varied degrees.
  • Condensation affects protein accessibility for DNA transcription.
  • Heterochromatin (tightly packed) — inactive
  • Euchromatin (loosely packed) — active

Epigenetic Regulation (continued)

  • Changes in chromatin structure alter transcription without altering DNA sequence. These mechanisms include:
    • DNA methylation
    • Histone modification
    • Chromatin remodeling
    • Non-coding RNA synthesis

DNA Methylation

  • Methylation adds a methyl group to cytosine.
  • Formation 5-methylcytosine due to participating of DNA methyltransferases
  • In vertebrates limited to CpG sequences (cytosine next to guanosine)
  • About 60% of cytosine nucleotides in mammals are methylated and recognized by MBD proteins (Methyl-CpG Binding Domain).
  • Methylation causes closure of chromatin area and blocks gene transcription.
  • Examples relate to cellular identity, X-chromosome inactivation, gene reprogramming, and genomic imprinting

Cellular Identity

  • DNA methylation patterns pass through cell division
  • Conservative methyltransferases interact with unmethylated strands for methylation of CpG sequences

X-chromosome inactivation

  • In female mammals, one X chromosome is inactivated in each cell.
  • Inactivation occurs randomly and is passed to daughter cells (e.g., calico cats)

Epigenetic Reprogramming

  • Methylation patterns erased in germline
  • Paternal and maternal methylation imprinted after development

Chromatin Structure

  • DNA and proteins form chromatin, which can condense
  • Condensed chromatin (heterochromatin) — transcriptionally inactive
  • Loose chromatin (euchromatin) — transcriptionally active

Histone Modification

  • Nucleosome histones can be modified covalently.
  • Common modifications — phosphorylation, acetylation, methylation, ubiquitination
  • Modified amino acids numbered (36 of H3 near the N-terminus), can be methylated
  • Modification patterns can be propagated through cell division and influence function of proteins.

Histone Modification (continued)

  • Histone acetylation — increases gene expression by relaxing chromatin
  • Histone deacetylation — reduces gene expression by tightening chromatin

Histone Modification (continued)

  • Methylation on lysines has different effects
  • Increased expression: H3 K4 me3, K36 me3, K79 me3
  • Decreased expression: H3 K9 me3, K27 me3, H4 K20 me3

Histone Modification (continued)

  • During DNA replication, histones are distributed randomly to daughter chromosomes.
  • Proteins responsible for histone modifications keep the patterns by binding, adding modifications

Chromatin Remodeling

  • Involves condensation/loosening of chromatin
  • Used by histone/chromatin-modifying complexes to influence gene expression

Chromatin Remodeling (continued)

  • Gene activators/repressors recruit proteins to promoters for specific interactions — e.g., histone acetyltransferase (adds acetyl groups), histone deacetylase (removes acetyl groups)

Chromatin Remodeling (continued)

  • Modifications in regions can propagate.
  • Barrier sequences block the spread

Histone Octamer Shift

  • A chromatin remodeling mechanism involves shifting histone octamers to alter DNA access.
  • ATP dependent remodeling protein complexes cause DNA loosening and movement.

Regulatory RNA

  • Noncoding RNAs, such as miRNAs, siRNAs, and IncRNAs, play diverse roles in regulating gene expression.

mi RNAs

  • miRNA is small hairpin RNA that is processed.
  • Single-stranded miRNA, protein complex (RNA-induced silencing complex, RISC)
  • RISC recognizes complementary bases in the target mRNA and can degrade or reduce translation by mRNA

si RNA

  • formed from double-stranded (usually exogenous/endogenous) large RNA
  • Cleaved by protein DISCER
  • Forms siRNA-RITS complex that attaches to pre-mRNA
  • Transcription elongation inhibited

IncRNA

  • Long non-coding RNAs (IncRNAs) are more than 200 nucleotides long.
  • Xist (17,000 nucleotides) plays a key role in inactivating one of the two X chromosomes.
  • Some IncRNAs fold into specific structures and place proteins on DNA/RNA sequences

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Related Documents

Lec 8 Updated Gene Expression Control PDF

Description

This quiz explores the roles of mediators, general transcription factors (GTFs), and specific transcription factors (STFs) in gene regulation. Additionally, it covers mechanisms such as enhancer/silencer interactions, transcription regulators, and combinatorial control. Test your knowledge on these essential components of transcription.

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