BMS 141 Lecture 12: Gene Expression Regulation

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Questions and Answers

What is the primary function of protein kinase A in the activation of gene expression through cAMP?

  • Inhibition of transcription factors
  • Degradation of mRNA
  • Binding of RNA polymerase
  • Phosphorylation of CREB (correct)

How is the transferrin receptor mRNA stabilized during low iron concentrations?

  • By acetylation of mRNA
  • By increased mRNA synthesis
  • By trans-acting iron regulatory proteins (IRPs) (correct)
  • By binding of iron itself

Which component binds specifically to the response element GRE in the context of steroid hormones?

  • Hormone/receptor complex (correct)
  • RNA polymerase
  • Basal transcription factors
  • Coactivators

What is one of the mechanisms through which gene expression can be regulated at the DNA level in eukaryotes?

<p>Histone acetylation (A)</p> Signup and view all the answers

Which phenomenon can lead to drug resistance in eukaryotic cells?

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

What is the purpose of mRNA editing in intestinal cells concerning Apo B mRNA?

<p>To create a shorter protein that functions in chylomicron formation. (A)</p> Signup and view all the answers

Which codon undergoes editing in the Apo B mRNA to switch the encoded amino acid from glutamine to a stop codon?

<p>Codon 2153. (D)</p> Signup and view all the answers

Which of the following best describes the relationship between Apo B-100 and Apo B-48 proteins?

<p>Both proteins are produced from the same primary mRNA transcript. (D)</p> Signup and view all the answers

What type of modification occurs in mRNA editing for the Apo B gene in intestinal cells?

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

What does the difference in size between Apo B-100 and Apo B-48 proteins indicate about their synthesis?

<p>They are produced through distinct posttranscriptional modifications. (B)</p> Signup and view all the answers

What role do general (basal) transcription factors play in transcription initiation?

<p>Bind to promoter sequences to recruit RNA polymerase (A)</p> Signup and view all the answers

Which type of transcription factors bind to enhancer sequences?

<p>Specific transcription factors (A)</p> Signup and view all the answers

How do specific transcription factors modulate the efficiency of transcription initiation?

<p>By interacting with both basal transcription factors and RNA polymerase (C)</p> Signup and view all the answers

What is the primary function of coactivator proteins in transcription regulation?

<p>To interact with specific transcription factors (A)</p> Signup and view all the answers

Which of the following mechanisms does NOT contribute to the regulation of transcription?

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

What is required for the bending of the DNA molecule in transcription regulation?

<p>Specific transcription factors bound to DNA (B)</p> Signup and view all the answers

Which of the following best describes constitutive genes?

<p>Genes that are continually expressed for basic functions (A)</p> Signup and view all the answers

What defines the specific transcription factors as activators or repressors?

<p>Their binding to enhancer and silencer sequences (C)</p> Signup and view all the answers

What type of gene expression is influenced by DNA-related mechanisms in eukaryotes?

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

What is the function of enhancer sequences in gene transcription?

<p>To facilitate the binding of specific transcription factors (activators) (D)</p> Signup and view all the answers

What type of epigenetic mechanism modifies DNA accessibility to transcription machinery?

<p>Chromatin acetylation/deacetylation (C)</p> Signup and view all the answers

Trans-acting factors are characterized by which of the following?

<p>Being encoded by different genes and synthesized in the cytosol (C)</p> Signup and view all the answers

Which statement regarding regulated genes is accurate?

<p>Their expressions are controlled by environmental conditions (A)</p> Signup and view all the answers

Silencer sequences serve to:

<p>Repress transcription by binding specific transcription factors (B)</p> Signup and view all the answers

How does control at the level of posttranslational processes differ from transcriptional control?

<p>It involves modification of proteins after translation (C)</p> Signup and view all the answers

Which of the following describes a key characteristic of transcriptional control?

<p>It involves DNA-encoded sequences that affect RNA synthesis (C)</p> Signup and view all the answers

What form of chromatin is associated with actively transcribed genes?

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

What effect does acetylation of histone proteins have on chromatin structure?

<p>Decreases interaction with negatively charged DNA (B)</p> Signup and view all the answers

Which process reverses the effect of histone acetylation?

<p>Histone deacetylation (A)</p> Signup and view all the answers

What is the function of DNA methyltransferase in gene expression?

<p>Methylates cytosines at CpG sites (C)</p> Signup and view all the answers

How does DNA methylation directly affect transcription?

<p>Inhibits binding of transcriptional factors (C)</p> Signup and view all the answers

What is primarily observed in transcriptionally active chromatin?

<p>High levels of acetylation (C)</p> Signup and view all the answers

What typically precedes the methylation of cytosines in vertebrate DNA?

<p>Guanine bases (A)</p> Signup and view all the answers

What is the main effect of chromatin remodeling on transcription machinery?

<p>Facilitates access to the promoter regions (C)</p> Signup and view all the answers

Flashcards

Chromatin Remodeling

A process that alters the structure of chromatin, making DNA more or less accessible for transcription.

Euchromatin

The relaxed form of chromatin where DNA is more accessible for transcription.

Heterochromatin

The tightly packed form of chromatin where DNA is less accessible for transcription.

Histone Acetylation

The addition of an acetyl group to a lysine residue on the histone tail.

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Histone Deacetylation

The removal of an acetyl group from a lysine residue on the histone tail.

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DNA Methylation

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

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DNA Demethylation

The removal of a methyl group from a cytosine base in DNA.

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Promoter

A region of DNA that controls the start of transcription.

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Constitutive genes

Genes that are continuously expressed, essential for fundamental cellular processes.

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Regulated genes

Genes whose expression is regulated, turned on or off depending on specific conditions.

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Transcription

The synthesis of RNA using a DNA template; the first step in gene expression.

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Cis-acting elements

DNA sequences that regulate gene expression by serving as binding sites for proteins.

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Promoter sequences

DNA sequences located upstream of the transcription start site, binding basal transcription factors and RNA polymerase, initiating transcription.

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Enhancer sequences

DNA sequences that enhance transcription by binding specific transcription factors (activators).

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Silencer sequences

DNA sequences similar to enhancers but bind repressors, hindering transcription.

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Trans-acting transcription factors

Proteins encoded by other genes, synthesized in the cytoplasm, and then translocated to the nucleus to regulate transcription.

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Specific Transcription Factors

Proteins that bind to specific DNA sequences called enhancers or silencers to modulate the efficiency of transcription initiation.

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Co-activators

Proteins that interact with specific transcription factors and help regulate transcription. They don't directly bind to DNA.

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Basal Transcription Factors

Proteins that bind to promoter sequences and facilitate the assembly of the transcription initiation complex, recruiting RNA polymerase.

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Enhancers

DNA sequences located at a distance from the promoter that can influence gene expression by interacting with specific transcription factors.

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Silencers

DNA sequences located at a distance from the promoter that can repress gene expression by interacting with specific transcription factors.

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Epigenetics

Inherited changes in gene expression that are not caused by changes in DNA sequence. It can involve chromatin remodeling and DNA methylation.

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Cell-surface hormone

A type of hormone that binds to receptors on the cell surface, triggering a chain of events that ultimately lead to changes in gene expression.

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cAMP

A cyclic nucleotide that acts as a second messenger in signal transduction pathways, often involved in activating protein kinase A.

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Protein kinase A

A family of enzymes that phosphorylate target proteins, altering their activity and influencing cellular processes.

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CREB

A transcription factor that binds to cAMP response elements (CRE) in the promoter region of genes, promoting gene expression.

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CRE (cAMP response element)

A DNA sequence within a gene's promoter region that binds CREB, triggering transcription.

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What is mRNA editing?

A process where the genetic code of an mRNA molecule is altered after it has been fully processed. This can change the amino acid sequence of the protein produced.

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What happens in Apo B mRNA editing?

A specific example of mRNA editing where a cytosine nucleotide in the mRNA sequence is converted to uracil. This changes the codon from CAA (glutamine) to UAA (stop codon), resulting in a shorter protein product.

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What are Apo B-100 and Apo B-48?

The protein produced from the apolipoprotein B (Apo B) gene is important for transporting lipids in the blood. Apo B-100 is the full-length protein produced in the liver, while Apo B-48 is a shorter version produced in the small intestine.

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What is deamination of cytosine?

A key step in mRNA editing. It involves changing a cytosine (C) base to a uracil (U) base in the Apo B mRNA.

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How does mRNA editing contribute to tissue diversity?

The process of mRNA editing can result in tissues producing different protein isoforms from the same gene. This allows for specialized functions in different parts of the body.

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Study Notes

Course Information

  • Course: BMS 141
  • Lecture Number: 12
  • Title: Regulation of Gene Expression
  • Instructor: Dr. Lamees Dawood
  • Program: Medicine and Surgery
  • Semester: Fall 2024
  • University: Galala University (Powered by Arizona State University)

Gene Regulation: Different Control Sites

  • Regulation occurs at various levels:
    • Transcriptional level
    • Posttranscriptional mRNA level
    • Posttranslational level
    • DNA-related mechanisms in eukaryotes

Constitutive vs. Regulated Genes

  • Constitutive (housekeeping) genes:
    • Continuously expressed
    • Encode proteins for basic cellular functions
  • Regulated genes:
    • Expressed only under specific conditions
    • Expressed in all cells or a subset
    • Expression regulated by factors like where, when and how much

Transcriptional Level Regulation

  • Synthesis of RNA directed by DNA-dependent RNA polymerase
  • Cis-acting elements: DNA sequences on the same chromosome as the gene, regulating its transcription

Cis-Acting DNA Sequences

  • Promoters:
    • Located upstream of the transcription start site (+1)
    • Binding sites for basal transcription factors and RNA polymerase
  • Enhancers:
    • Located upstream or downstream of the start site
    • Thousands base pairs away from the promoter
    • Binding sites for specific transcription factors (activators)
  • Silencers:
    • Similar to enhancers
    • Bind specific transcription factors (repressors)

Trans-Acting Transcription Factors (Protein Factors)

  • Encoded by different genes
  • Synthesized in the cytosol and move to nucleus
  • General (basal) factors:
    • Recognize and bind to promoter sequences
  • Specific factors (activators/repressors):
    • Bind to DNA sequences (enhancers/silencers) regulating transcription
    • Respond to different signals (e.g., hormones)
  • Co-activators:
    • Interact with specific transcription factors and control transcription activity
    • Do not bind to DNA

General or Basal Transcription Factors (TFs)

  • Bind to consensus sequences of promoters (e.g., CTF, SP1, TFIID)
  • Facilitate assembly of the initiation complex and recruitment of RNA polymerase II
  • Catalyze basal or constitutive transcription

Specific or Regulatory Transcription Factors (TFs)

  • Bind regulatory sequences (enhancers or silencers)
  • Modulate transcription initiation efficiency
  • Mediate responses to signals (e.g., hormones)
  • Regulate gene expression at specific times

Specific/Regulatory Mechanism

  • TFs interact with:
    • DNA sequences (enhancers/silencers)
    • General TFs and RNA polymerase II in the initiation complex
    • Coactivators (e.g., histone acetyltransferase)

DNA Bending

  • DNA bending can allow interaction between specific TFs and basal TFs and RNA polymerase II at promoter region
  • Specific TFs (bound to enhancer/silencer DNA sequences) interact distally (far from the promoter) with basal TFs

Epigenetic Mechanisms - Regulation of Transcription Control

  • Chromatin remodeling:
    • Acetylation and deacetylation by histone proteins
    • Acetylation reduces positive charge, increases accessibility and relaxed chromatin (euchromatin)
    • Deacetylation restores condensed chromatin (heterochromatin - inactive)
  • DNA methylation:
    • Addition of methyl groups to cytosine bases (CpG dinucleotides) at the gene promoter
    • Prevents binding of basal transcription factors
    • May recruit histone deacetylase, increasing heterochromatin formation

Euchromatin and its effect on Transcription

  • Following acetylation, nucleosomal removal, the promoter opens, becoming accessible to the transcription machinery, activating transcription

mRNA Posttranscriptional Regulation

  • Splice-site choice and differential tissue expression
  • mRNA editing: modifications after full processing (e.g., apo B mRNA)
  • mRNA stability
  • Coordinate gene expression in eukaryotes (influenced by hormonal factors, e.g., glucagon)

mRNA Editing (e.g., Apo B mrna)

  • Apo B mRNA (4563 codons) expressed in hepatocytes and small intestinal cells
  • Production of two different protein sizes (Apo B-100, Apo B-48) performing different functions in cell processes

Coordinate Expression in Eukaryotes (Hormonal effects)

  • Cell-surface hormones (e.g., glucagon) activate signal transduction
  • Regulation is influenced by protein kinase A (PKA) and other factors that activate CREB proteins which bind to CRE sequences in the promoter region, affecting gene expression

Regulation of mRNA Stability

  • Transferrin (iron transport protein)
  • When iron concentration is low, iron regulatory protein (IRP) binds to iron response elements (IRES) on transferrin mRNA
  • Stabilizing the mRNA, and increasing transferrin receptor synthesis
  • DNA accessibility (by transcription machinery): eg., chromatin remodeling, methylation
  • DNA copy number variation (e.g. drug resistance)
  • DNA rearrangements (e.g. Ig production)
  • Transcription machinery effects by DNA and transcription factors

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