Epigenetics Mechanisms Overview
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Questions and Answers

    • What are the two main categories that epigenetic mechanisms are divided into?

    Transcriptional and Post-transcriptional

    Which of the following is not a type of covalent histone modification?

  • Histone Deimination
  • Histone Acetylation
  • Histone Sumoylation
  • Histone Methylation
  • Histone Exchange (correct)

    • Histone methylation is irreversible and stable.

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

    What is the attachment of a methyl group (CH3) to cytosine in CpG dinucleotides called?

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

    What are the main types of DNA methyltransferases?

    <p>De Novo and Maintenance</p> Signup and view all the answers

    Epigenetic changes are always permanent and irreversible.

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

    Epigenetic changes can alter the DNA sequence.

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

    What is the process by which one X chromosome in female mammals becomes inactive called?

    <p>X chromosome inactivation</p> Signup and view all the answers

    What is the name of the condensed structure formed during X chromosome inactivation?

    <p>Barr body</p> Signup and view all the answers

    What is the name of the specific gene responsible for initiating and regulating X inactivation?

    <p>Xist gene</p> Signup and view all the answers

    What term is used to describe the suppression of an expressible gene?

    <p>Imprinting</p> Signup and view all the answers

    Genomic imprinting is an example of Mendelian inheritance.

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

    Which of the following syndromes is associated with a deletion in the Small nuclear ribonucleoprotein associated protein N gene's promoter and ICR on the paternal chromosome?

    <p>Prader-Willi syndrome (A)</p> Signup and view all the answers

    Which imprinted gene, primarily active in brain cells, is affected by a deletion in its ICR, leading to Angelman syndrome?

    <p>UBE3A gene</p> Signup and view all the answers

    Rubinstein-Taybi syndrome is a genetic disorder associated with alterations in the epigenetic histone code.

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

    Fragile X syndrome is caused by errors in the DNA methylation mechanism that affect repeat sequences.

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

    Which gene is responsible for mRNA transport and undergoes alterations when CGG repeats in its 5'UTR region exceed 200 copies, contributing to Fragile X syndrome?

    <p>FMR1 gene</p> Signup and view all the answers

    The term '______' was initially proposed by Conrad Waddington in 1942.

    <p>epigenetics</p> Signup and view all the answers

    What does the prefix 'epi' mean in Ancient Greek?

    <p>upon, over, or beyond</p> Signup and view all the answers

    Epigenetic regulation refers to changes in gene expression that are passed on through mitotic and/or meiotic cell division without altering the DNA's nucleotide structure.

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

    What distinguishes one individual from another?

    <p>genome</p> Signup and view all the answers

    What distinguishes one cell from another?

    <p>epigenome</p> Signup and view all the answers

    What remains the same in every cell of an organism?

    <p>DNA sequence</p> Signup and view all the answers

    Which of the following processes can vary among cells?

    <p>All of the above (D)</p> Signup and view all the answers

    Which of the following is NOT an example of an epigenetic mechanism?

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

    Epigenetic mechanisms can be divided into two categories. What are those categories?

    <p>Direct and Indirect control (D)</p> Signup and view all the answers

    Which of the following is NOT a covalent modification of histones?

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

    Which of the following is a non-covalent modification of histones?

    <p>Interaction with non-coding RNA (C)</p> Signup and view all the answers

    Histone modifications are always irreversible.

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

    What type of modifications are histone acetylation and phosphorylation?

    <p>reversible</p> Signup and view all the answers

    What is the function of histone acetyltransferase (HAT)?

    <p>add acetyl groups to histones</p> Signup and view all the answers

    What is the function of histone deacetylase (HDAC)?

    <p>remove acetyl groups from histones</p> Signup and view all the answers

    Histone methylation does not alter the charge of histones.

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

    Which of the following is NOT a known histone methylation enzyme?

    <p>Histone acetylase (HAT) (B)</p> Signup and view all the answers

    Histone methylation is a reversible process.

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

    Histone deimination is a modification that can contribute to chromatin compaction.

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

    Histone ubiquitination results in chromatin compaction.

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

    What is the function of histone sumoylation?

    <p>transcriptional repression</p> Signup and view all the answers

    Histone phosphorylation is a reversible process.

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

    Post-transcriptional mechanisms involve the inhibition of protein synthesis through the impact of non-coding RNA on non-coding mRNA.

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

    What are the two main types of non-coding RNAs involved in epigenetic processes?

    <p>miRNA and siRNA</p> Signup and view all the answers

    Only about 3 percent of the mammalian genome consists of protein-coding messenger RNAs (mRNA).

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

    Non-coding RNAs can initiate histone modifications and DNA methylation.

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

    SiRNA perfectly matches the target mRNA sequence and cleaves it, leading to the degradation of the mRNA.

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

    MiRNA usually cannot cleave mRNA because it doesn't exhibit perfect matching with mRNA.

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

    MiRNA can suppress translation by preventing the binding of initiation factors to mRNA.

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

    What is the most important modification at the DNA level?

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

    What is the role of CpG islands in housekeeping and regulatory genes?

    <p>resistant to DNA methylation</p> Signup and view all the answers

    CpG islands are typically resistant to DNA methylation.

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

    Heterochromatin regions are known to exhibit high levels of DNA methylation.

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

    DNA methylation is a reversible process.

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

    A methyl group is attached to thymine in CpG islands.

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

    DNA methylation can lead to gene silencing.

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

    What is the name of the enzyme responsible for adding a methyl group to the 5th carbon of cytosine in DNA?

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

    What happens when both strands of DNA are methylated?

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

    What happens when only one strand of DNA is methylated?

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

    De novo DNA methyltransferases are involved in replicating existing methylation patterns.

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

    Maintenance DNA methyltransferases are involved in preserving existing methylation patterns.

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

    Which of the following DNA methyltransferases is responsible for de novo methylation?

    <p>DNMT3A &amp; DNMT3B (C)</p> Signup and view all the answers

    Genetic changes are generally reversible.

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

    Genetic changes affect gene expression.

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

    Epigenetic changes affect the sequence of DNA.

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

    Epigenetic changes can be inherited across generations.

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

    Epigenetic modifications can be influenced by environmental factors.

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

    Epigenetic modifications are the only factor that determines the risk of cancer development.

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

    How does DNA methylation of tumor suppressor genes affect cancer development?

    <p>Inhibits their expression (B)</p> Signup and view all the answers

    How can DNA methylation and histone modifications contribute to cancer development?

    <p>All of the above (D)</p> Signup and view all the answers

    Epigenetic drug resistance, a phenomenon caused by epigenetic changes, can make cancer treatments less effective.

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

    Epigenetic therapies, such as DNA methylation inhibitors and HDAC inhibitors, aim to reverse epigenetic changes associated with cancer.

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

    MiRNA therapies are a potential treatment for cancer.

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

    Dosage compensation is a process that ensures equal dosage of genes on the X chromosome between the two sexes.

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

    Dosage compensation occurs in female mammals.

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

    Dosage compensation occurs during embryonic development.

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

    The inactive X chromosome is known as the Barr Body.

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

    X inactivation is a permanent process.

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

    The inactivation center (Xic) is a region on the Y chromosome.

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

    In humans, having two active X chromosomes is lethal during the embryonic period.

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

    The Xist gene is a long non-coding RNA responsible for X inactivation.

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

    Xist RNA coats the inactive X chromosome, leading to the silencing of genes in the X chromosome.

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

    The Tsix gene prevents X inactivation.

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

    The Xist and Tsix genes are transcribed in the same direction.

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

    A mutation in Tsix can result in the premature inactivation of one of the X chromosomes.

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

    Genetic imprinting is used to describe the suppression of an expressible gene.

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

    Genomic imprinting is a permanent change in the DNA sequence.

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

    What is the primary cause of Prader-Willi syndrome?

    <p>A deletion in the SNRPN gene (A)</p> Signup and view all the answers

    What is the primary cause of Angelman syndrome?

    <p>A mutation in the UBE3A gene (A)</p> Signup and view all the answers

    Rubinstein-Taybi syndrome is an autosomal dominant disorder characterized by broad thumbs and toes, short stature, cognitive impairment, and anomalies.

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

    Which gene is most closely associated with the development of Fragile X syndrome?

    <p>FMR1 (B)</p> Signup and view all the answers

    Fragile X syndrome is caused by an increased methylation of the FMR1 gene.

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

    Individuals with Fragile X syndrome only exhibit physical differences.

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

    Anyone with Fragile X syndrome will most likely have the same level of severity in their condition.

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

    Flashcards

    What is epigenetics?

    Epigenetics refers to changes in gene expression without altering the DNA sequence. It's like a switch that controls how a gene behaves, not its actual DNA code.

    What is the epigenome?

    The epigenome is the collection of chemical modifications that influence gene expression in a cell. It's like a set of instructions for how a gene should be used.

    Describe DNA methylation.

    DNA methylation is a process where a methyl group (CH3 ) attaches to cytosine in DNA. It's like adding a sticky note to a gene, which can silence it and prevent it from being expressed.

    What are CpG islands?

    CpG islands are regions of DNA with high concentrations of cytosine-guanine (CpG) dinucleotides. They are often found in gene promoters and play a role in gene regulation.

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    Explain histone acetylation.

    Histone acetylation involves attaching an acetyl group to a histone protein, making the DNA more accessible to transcription factors. It's like loosening the DNA, allowing genes to be expressed.

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    What is histone methylation?

    Histone methylation is the attachment of a methyl group to a histone protein. It can either activate or repress gene expression depending on the specific residue.

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    Describe histone deimination.

    Histone deimination is the conversion of arginine residues in a histone protein to citrulline. It can affect chromatin structure and gene expression.

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    What is histone ubiquitination?

    Histone ubiquitination involves attaching ubiquitin, a small protein, to a histone. It can modify chromatin structure and regulate gene expression.

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    Explain histone sumoylation.

    Histone sumoylation is the attachment of a SUMO protein to a histone. It typically leads to transcriptional repression.

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    What is histone phosphorylation?

    Histone phosphorylation involves adding a phosphate group to a histone. It can influence chromatin structure and gene expression by interacting with other proteins.

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    What are non-covalent histone modifications?

    Non-covalent histone modifications include histone exchanges, interactions with non-coding RNAs, and chromatin repair. These modifications influence chromatin dynamics and gene regulation.

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    What are non-coding RNAs (ncRNAs)?

    Non-coding RNAs (ncRNAs) are RNA molecules that don't code for proteins. They play a crucial role in epigenetic regulation by influencing gene expression.

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    What are microRNAs (miRNAs)?

    MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by binding to messenger RNAs (mRNAs) and suppressing their translation.

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    What are small interfering RNAs (siRNAs)?

    Small interfering RNAs (siRNAs) are short double-stranded RNA molecules that can silence gene expression by causing degradation of the target messenger RNA (mRNA).

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    What is RNA interference (RNAi)?

    RNA interference (RNAi) is a biological process by which small RNA molecules, such as siRNAs and miRNAs, regulate gene expression. It involves the silencing or degradation of target mRNAs.

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    What are DNA methyltransferases (DNMTs)?

    DNA methyltransferases (DNMTs) are enzymes responsible for adding methyl groups to DNA. They play a crucial role in DNA methylation, an epigenetic modification that can regulate gene expression.

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    What are de novo DNA methyltransferases?

    De novo DNA methyltransferases (DNMT3A and DNMT3B) establish new methylation patterns in DNA, typically during development and cell division.

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    What are maintenance DNA methyltransferases?

    Maintenance DNA methyltransferases (DNMT1) copy existing methylation patterns to newly synthesized DNA during replication, ensuring the inheritance of methylation patterns.

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    What is dosage compensation?

    Dosage compensation refers to mechanisms that equalize gene expression between the sexes, particularly in organisms with sex chromosomes like X and Y.

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    What is X chromosome inactivation?

    X chromosome inactivation is a process where one X chromosome in female mammals becomes inactive, ensuring equal gene expression between males and females.

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    What is the Barr body?

    The Barr body is a highly condensed inactive X chromosome found in the nuclei of female somatic cells. It's visible during interphase and represents the silenced X chromosome.

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    What is the X inactivation center (Xic)?

    The X inactivation center (Xic) is a region on the X chromosome that plays a critical role in initiating and regulating X inactivation.

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    What is the Xist gene?

    The Xist gene is a non-coding gene located within the X inactivation center (Xic). It produces a long non-coding RNA that coats the inactive X chromosome, leading to its silencing.

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    What is the Tsix gene?

    The Tsix gene is a non-coding gene located within the X inactivation center (Xic) that functions to prevent X inactivation. It's the opposite of Xist and helps maintain the active state of one X chromosome.

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    What is genomic imprinting?

    Genomic imprinting is an epigenetic phenomenon where the expression of certain genes is determined by the parent of origin. It's like a tag that marks whether a gene came from the mother or father.

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    What are imprinting control regions (ICRs)?

    Imprinting control regions (ICRs) are DNA sequences that regulate imprinted genes. They can act as switches, turning imprinted genes on or off depending on the parent of origin.

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    What is Prader-Willi syndrome?

    Prader-Willi syndrome is a genetic disorder caused by a deletion or disruption of genes on chromosome 15, specifically on the paternal allele. It's characterized by developmental delay, obesity, and other features.

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    What is Angelman syndrome?

    Angelman syndrome is a genetic disorder caused by a deletion or disruption of genes on chromosome 15, specifically on the maternal allele. It's characterized by developmental delay, movement disorders, and a happy demeanor.

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    What is Rubinstein-Taybi syndrome?

    Rubinstein-Taybi syndrome is a genetic disorder characterized by broad thumbs and toes, short stature, cognitive impairment, and other features. It's often linked to mutations in histone acetyltransferases.

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    What is Fragile X syndrome?

    Fragile X syndrome is a genetic disorder caused by an expansion of CGG repeats in the FMR1 gene. This expansion can lead to silencing of the gene due to methylation.

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    What is DNA methylation?

    DNA methylation is the addition of a methyl group (CH3) to cytosine in DNA, often leading to gene silencing. It's like attaching a sticky note to a gene, preventing it from being read.

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    What is histone acetylation?

    Histone acetylation is the attachment of an acetyl group to a histone protein, making DNA more accessible to transcription factors. It's like loosening the DNA, allowing genes to be expressed.

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    Study Notes

    Epigenetic Mechanisms

    • Epigenetics examines changes in gene expression without altering the DNA sequence.
    • Epigenetic regulation is crucial for development and differentiation.
    • Epigenetic mechanisms can be broadly categorized into those that directly influence gene expression (transcriptional) and those that indirectly impact it (post-transcriptional, mRNA silencing).

    Mechanisms Directly Controlling Gene Expression

    • DNA Methylation: Methylation occurs when a methyl group attaches to cytosine in CpG dinucleotides. This is a common modification, and its impact often results in gene silencing. Methylation frequently occurs at CpG islands, influencing gene expression in a variety of biological processes, including those related to gene activation and inactivation.
    • Histone Modifications: These involve covalent changes to histone proteins (e.g., acetylation, methylation, deimination, phosphorylation). Acetylation generally promotes gene expression, while methylation and deimination can either activate or repress it, depending on the specific residue and context. Ubiquitination is another mechanism by which larger molecular changes can be brought to histone structures. Sumoylation, a modification associated with ubiquitination involves the attachment of small ubiquitin-like modifier (SUMO) molecules to lysine residues of histones. This is primarily linked to gene repression.
    • Chromatin Modifications (Non-Covalent): These encompass interactions with small non-coding RNAs (e.g. miRNA, siRNA), histone exchanges, histone deposition, interactions with other agents (like viruses), chromatin repair, and interactions with chromatin remodeling factors.

    Mechanisms Indirectly Controlling Gene Expression

    • Post-transcriptional mechanisms primarily involve the inhibition of protein synthesis through the interactions of non-coding RNAs with mRNA. Specific examples include small interfering RNA (siRNA) and microRNA (miRNA).

    DNA Modifications

    • DNA Methylation: A significant type of DNA modification, often linked with gene silencing. This occurs at CpG islands, which are short sequences of cytosine and guanine nucleotides.
    • CpG Islands: Regions rich in CpG sequences typically associated with actively transcribed genes. In contrast, regions with limited CpG content are often associated with silenced genes.

    Histone Modifications

    • Histone Acetylation: Acetylation of lysine residues on histones generally promotes gene activation by reducing the DNA-histone attraction. Enzymes like histone acetyltransferase (HAT) introduce acetyl groups.
    • Histone Methylation: The addition of methyl groups to histones has variable effects. Mono-, di-, or tri-methylation often alter the binding of proteins to genes, affecting transcriptional activity. Histone methyltransferases (HMTs) add the methyl groups.
    • Histone Deimination: This involves the conversion of arginine to citrulline reducing the positive charge. This alteration usually promotes chromatin relaxation and gene expression, but in specific contexts, it can contribute to chromatin compaction.
    • Histone Phosphorylation: Phosphates bind to histones through specific amino acids (serine, threonine, tyrosine). This process is reversible, and phosphorylation can influence gene expression depending on the context.
    • Histone Ubiquitination: The attachment of ubiquitin in a complex process involving enzymes (E1, E2, and E3), can have diverse outcomes. In essence, it typically leads to chromatin relaxation and gene activation.
    • Histone Sumoylation: Sumoylation, the attachment of small ubiquitin-like modifier (SUMO) proteins, is a modification mostly linked to gene repression.

    Epigenetic Mechanisms and Cancer

    • Epigenetic changes, such as DNA methylation and histone modifications, play significant roles in cancer development. They often impact tumor suppressor genes (silencing them) or oncogenes (activating them) leading to uncontrolled cell division and tumor growth. Specific examples include hypermethylation of tumor suppressor genes, and the activation of oncogenes by DNA methylation and histone modifications. Genomic instability can be impacted by epigenetic mechanisms, impairing DNA damage repair genes.. Certain epigenetic changes may confer resistance to cancer treatments.

    Treatment and Epigenetic Regulation

    • Therapies targeting epigenetic changes are gaining prominence. Current approaches include DNA methylation inhibitors (acting on DNA methyltransferases) and histone deacetylase (HDAC) inhibitors, that help regulate gene expression. miRNA therapies are also an emerging area of interest, aiming to correct abnormal miRNA expression.

    Epigenetic Events

    • Epigenetic mechanisms regulate gene expression or suppression without modifying the DNA's underlying sequence and play a vital role in several biological processes, including genomic imprinting, gametogenesis, and cellular rejuvenation. Genomic imprinting is a specific type, where the activity of a gene is determined by its parental origin. Notably, some imprinted genes have distinct methylation patterns (correlated to either a maternal or paternal allele's characteristics).

    Dosage Compensation (X Chromosome Inactivation)

    • Dosage compensation ensures an equal expression level of X chromosomes between males and females. In female mammals, one X chromosome becomes inactive in each cell to equalize the expression level with males. This process is a crucial example of epigenetic control.

    X Chromosome Inactivation

    • During X chromosome inactivation, a highly condensed structure known as the Barr body forms due to DNA condensation, leading to a silencing of many of the genes carried on the inactive X chromosome. This process is driven by the Xist gene that leads to the X chromosome becoming inactive. Tsix is a second gene that interferes with the formation of the silencing complex.

    Xist and Tsix

    • Xist and Tsix genes play key roles in the X-chromosome inactivation process; Xist RNA is a key player in silencing the genes on the inactive X chromosome. Tsix functions to prevent X inactivation by overlapping with the Xist gene and transcribing in the opposite direction.

    Genetic Imprinting

    • Imprinting is a critical epigenetic mechanism with impact on the expression of genes determined by their parental origin, resulting in differential gene expression depending on whether a gene is inherited from the mother or father. In genomic imprinting, certain genes are silenced based on whether they are received from the mother or father. Specific examples include syndromes like Prader-Willi and Angelman syndromes that arise from abnormal imprinting on chromosome 15. These conditions are caused, for example, by a deletion in the ICR or the UBE3A gene on chromosome 15.

    Fragile X Syndrome

    • Errors in DNA methylation can accompany repeat disorders, including fragile X syndrome, characterized by a variety of intellectual and behavioral alterations. The repeat sequence abnormalities associated with Fragile X syndrome can lead to abnormal methylation in the FMR-1 gene, which is related to mRNA transport..

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    Description

    Explore the fascinating world of epigenetics, where gene expression changes occur without alterations to the DNA sequence. This quiz delves into mechanisms like DNA methylation and histone modifications that regulate gene expression during development. Test your knowledge on how these processes play a crucial role in gene silencing and expression.

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