Genome and Chromatin Structure Quiz
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Questions and Answers

Which of the following levels of gene expression regulation involves changes to chromatin structure?

  • Genome/chromatin structure (correct)
  • Regulation via non-coding RNAs
  • Translation regulation
  • Post-transcriptional regulation
  • What is the primary role of DNA methylation in gene expression?

  • Associated with transcriptional repression (correct)
  • Inhibits transcriptional repression
  • Promotes transcription factor binding
  • Facilitates chromatin remodeling
  • Which of the following best describes the process of X-inactivation?

  • It occurs only in males during embryogenesis.
  • It leads to the activation of both X chromosomes.
  • It balances expression of X-linked genes in females. (correct)
  • It results in random expression of X-linked genes.
  • What role do chromatin binding proteins play in transcription?

    <p>They recognize epigenetic marks to establish chromatin states.</p> Signup and view all the answers

    How does the epigenetic profile affect transcriptional regulation?

    <p>It dictates the accessibility of DNA to transcription factors.</p> Signup and view all the answers

    What is a characteristic of CpG islands related to gene regulation?

    <p>They are often found in gene-rich areas and remain unmethylated.</p> Signup and view all the answers

    What is a feature of transcription regulation at the post-transcriptional level?

    <p>Modifies RNA after its synthesis.</p> Signup and view all the answers

    What impact do non-coding RNAs have on gene expression?

    <p>They can bind DNA and proteins, influencing chromatin structure.</p> Signup and view all the answers

    What role does X inactivation specific transcript (XIST) play in gene regulation?

    <p>It binds to the chromosome that will be inactivated.</p> Signup and view all the answers

    Which mechanism is primarily responsible for transcriptional regulation at mammalian gene promoters?

    <p>Chromatin remodeling complexes allowing access to transcription factors.</p> Signup and view all the answers

    What is a characteristic of enhancers in gene expression?

    <p>They facilitate cell- and tissue-specific gene expression.</p> Signup and view all the answers

    How do transcription factors interact with the transcription process?

    <p>They allow DNA polymerase access to the promoter.</p> Signup and view all the answers

    What is the significance of alternative promoters in mammalian genes?

    <p>They contribute to the potential for diverse transcript variants.</p> Signup and view all the answers

    What is the role of p-TEFb in transcription elongation?

    <p>It phosphorylates DNA polymerase to enable continued elongation.</p> Signup and view all the answers

    How do non-coding RNAs (ncRNAs) influence transcription?

    <p>They can interfere with sense transcription and modify histone codes.</p> Signup and view all the answers

    What is one of the key features of Waddington’s epigenetic landscape?

    <p>It illustrates how master transcription factors regulate subordinate factors.</p> Signup and view all the answers

    What condition is caused by mutations in the regulatory open reading frame upstream of the primary ORF in the TPO gene?

    <p>Marie Unna hereditary hypotrichosis</p> Signup and view all the answers

    How does the pRNA contribute to the silencing of rDNA loci?

    <p>By directing DNMT3b for de novo methylation</p> Signup and view all the answers

    What type of genetic change results in atrichia with papular lesions?

    <p>Recessive mutations in the TPO gene</p> Signup and view all the answers

    What is the role of PAPAS in rDNA silencing?

    <p>To promote nucleosome sliding and repression</p> Signup and view all the answers

    Which of the following is NOT involved in the transcriptional regulation of gene expression in eukaryotes?

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

    Which type of RNA is primarily involved in the control of rRNA gene expression?

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

    What is one function of transcriptional corepressors mentioned in the context of TPO gene regulation?

    <p>Inhibiting the activity of nuclear receptors</p> Signup and view all the answers

    What is a common result of transcriptional regulation through non-coding RNAs?

    <p>Decreased protein synthesis</p> Signup and view all the answers

    How does the antisense transcript ANRIL affect the CDKN2B–CDKN2A locus?

    <p>It induces H3K27me leading to repression</p> Signup and view all the answers

    Which of the following describes the function of HOX transcript antisense RNA (HOTAIR)?

    <p>It recruits PRC2 to silence the HOXD locus</p> Signup and view all the answers

    What role do splicing enhancers and suppressors play in alternative splicing?

    <p>They can create stronger or weaker splice sites</p> Signup and view all the answers

    Which statement about the IRP/IRE system is correct?

    <p>In iron-depleted cells, IRPs bind to 5' UTR to repress translation</p> Signup and view all the answers

    What is the impact of RNA-binding regulatory proteins on mRNA structure?

    <p>They form complex structures that block ribosome advancement</p> Signup and view all the answers

    Which mechanism is utilized by ncRNAs such as miRNAs to regulate gene expression?

    <p>They repress expression by binding to the 3’ UTR</p> Signup and view all the answers

    What kind of modifications can antisense transcripts make to their associated sense promoters?

    <p>They can deposit H3K4me2, altering transcription regulation</p> Signup and view all the answers

    What effect do poison exons have in alternative splicing?

    <p>They cause the degradation of the spliced mRNA</p> Signup and view all the answers

    Study Notes

    Genome and Chromatin Structure

    • Transcription takes place in euchromatic DNA.
    • CTCF protein defines the boundaries between euchromatic and heterochromatic regions.
    • Chromosome territories are positioned within the nucleus, with those closer to the nuclear envelope being silenced.
    • Topologically associating domains (TADs) are distinct in different cell types, with different profiles of active and inactive TADs.
    • Non-coding RNAs (ncRNAs) can bind to DNA and proteins that bind to DNA or RNA, impacting chromatin structure.
    • ncRNAs can recruit chromatin remodeling complexes, which alter chromatin structure.

    Epigenetic profile and imprinting

    • Epigenetic mechanisms, including histone modifications, nucleosome positioning, and DNA methylation, play a role in gene expression.
    • The epigenetic profile is linked to chromatin structure, with chemical modifications of histones creating various chromatin states with different transcriptional activity levels.
    • Chromatin-binding proteins recognize epigenetic marks and contribute to establishing open or closed chromatin.

    DNA Methylation

    • DNA methylation (addition of methyl groups to cytosine bases in CpG dinucleotides) is associated with transcriptional repression.
    • Methylated DNA cannot be bound by transcription factors.
    • Specific proteins bind to methylated DNA, influencing chromatin organization and epigenetic maintenance.
    • Epigenetic memory is transmitted through mitosis due to the action of DNA methyltransferase 1 (DNMT1).
    • CpG islands in gene-rich areas remain unmethylated.
    • During gametogenesis, the epigenome is reset to a totipotent state.

    Imprinting

    • Around 150 genes in humans exhibit imprinting, meaning they are differentially expressed depending on whether they are inherited from the mother or father.
    • A common mechanism is methylation of the maternal differentially methylated region (DMR).

    X-Inactivation

    • During early embryogenesis, one of the X chromosomes in females undergoes X-inactivation, a process involving epigenetic modification.
    • Random X inactivation occurs in the blastula stage to ensure balanced expression of X-linked genes.
    • Epigenetic marks established during X inactivation persist through mitosis, contributing to the phenomenon of epigenetic memory.
    • The X inactivation center (XIC) is a 1 Mb region on the X chromosome, containing a 19 kb non-coding RNA called X inactivation specific transcript (XIST) that plays a key role in X inactivation.

    Transcriptional Regulation

    • Promoters are often devoid of nucleosomes to enable the assembly of the pre-initiation complex (PIC).
    • Chromatin remodeling complexes reposition nucleosomes, making promoters accessible to transcription machinery.
    • Many mammalian genes have alternate promoters, contributing to the diversity of gene expression.
    • Enhancers, often cell- and tissue-specific regulatory elements, can interact with promoters, contributing to precise gene control.
    • DNA looping, facilitated by cohesin and mediator proteins, is essential for enhancer-promoter interactions.
    • TAD structure can influence interactions between regulatory elements.
    • A vast number of transcription factors (general and tissue-specific) contribute to development, cell identity, and gene expression.
    • As cells differentiate, they exhibit increased epigenetic restriction.

    Transcriptional Elongation

    • Transcription factors can bind to promoters, but elongation may not proceed.
    • TFIIH facilitates the access of DNA polymerase to the promoter.
    • Phosphorylation of DNA polymerase by p-TEFb is required for efficient transcription elongation beyond abortive transcription.

    Transcription Termination

    • The polyadenylation signal (PAS) marks the termination site for RNA polymerase II.
    • Many mammalian genes utilize alternative cleavage and polyadenylation sites.

    Non-coding RNAs (ncRNAs) in Transcriptional Regulation

    • Antisense and bidirectional transcription of ncRNAs can interfere with sense transcription, affect DNA methylation, modify the histone code, or induce heterochromatic states.
    • ncRNAs also participate in the silencing of transposons.

    Post-Transcriptional Regulation

    • Alternative splicing: Enhancer and suppressor sequences modulate the strength of splice sites, leading to tissue-specific isoforms.
    • RNA turnover: The degradation of mRNA can be influenced by various factors, impacting gene expression levels.
    • RNA editing: Modifications to the RNA sequence, such as base substitutions or insertions, can alter the final protein product.

    Regulation of Translation

    • Leader peptides: Upstream open reading frames (uORFs) found in about one-third of human transcripts can influence translation initiation at the main ORF.
    • mRNA structure: Stem-loop structures in mRNA can affect ribosome movement and contribute to translational regulation.
    • RNA-binding proteins: These proteins can bind to mRNA and regulate translation initiation or elongation rates.

    ncRNAs in Translational Regulation

    • miRNAs, siRNAs, and piRNAs can repress the expression of target mRNAs.
    • miRNAs can specifically bind to the 3’ UTR of target mRNAs, modulating their translation efficiency.
    • Competition for binding sites on target mRNAs between different miRNAs creates a complex regulatory network of subtle effects.

    Cellular Iron Homeostasis

    • The iron responsive element (IRE)/iron regulatory protein (IRP) system plays a critical role in regulating cellular iron levels.
    • IRP1 and IRP2 proteins bind to IREs in the 5' UTR or 3' UTR of mRNAs, influencing their translation and stability.
    • In iron-deficient cells, IRPs bind to IREs in the 5' UTR, repressing translation.
    • In the same scenario, binding to IREs in the 3' UTR stabilizes the mRNA.
    • When iron levels are high, IRP binding is disrupted, leading to increased translation and mRNA degradation.

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    Test your knowledge on genome and chromatin structure, focusing on transcription, boundary definition by CTCF protein, and the impact of non-coding RNAs on chromatin. Explore the concepts of epigenetic profiles and imprinting, along with histone modifications and their role in gene expression.

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