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Questions and Answers
What is the primary function of histone tail modifications?
What is the primary function of histone tail modifications?
- To block access to chromatin DNA
- To create binding sites for transcription factors (correct)
- To facilitate histone-histone interactions
- To increase chromatin compaction
What is the correlation between chromatin packing and gene expression levels?
What is the correlation between chromatin packing and gene expression levels?
- Highly packed chromatin is associated with low gene expression
- Loosely packed chromatin is associated with high gene expression (correct)
- Loosely packed chromatin is associated with gene repression
- Highly packed chromatin is associated with high gene expression
What is the term used to describe the process of histone modifications regulating gene expression?
What is the term used to describe the process of histone modifications regulating gene expression?
- Chromatin remodeling
- Epigenetic regulation (correct)
- Post-translational modification
- Histone code hypothesis
Why must chromatin be made 'relaxed' before cellular machineries can access chromatin DNA?
Why must chromatin be made 'relaxed' before cellular machineries can access chromatin DNA?
What is the primary role of histone N-terminal tails?
What is the primary role of histone N-terminal tails?
What was the prevailing view of histones before the discovery of histone modifications?
What was the prevailing view of histones before the discovery of histone modifications?
What histone modification is associated with transcribed gene bodies?
What histone modification is associated with transcribed gene bodies?
Which histone modification is a mark of Polycomb-silenced promoters?
Which histone modification is a mark of Polycomb-silenced promoters?
What is the role of chromatin remodelers in the regulation of gene expression?
What is the role of chromatin remodelers in the regulation of gene expression?
Which histone modification is associated with active promoters?
Which histone modification is associated with active promoters?
What is the result of densely populated nucleosomes on transcription factor binding?
What is the result of densely populated nucleosomes on transcription factor binding?
What is the characteristic of active enhancers?
What is the characteristic of active enhancers?
What is the function of histone proteins in epigenetic regulation?
What is the function of histone proteins in epigenetic regulation?
What is the effect of DNA methylation on gene expression?
What is the effect of DNA methylation on gene expression?
What is the role of histone modifications in epigenetic regulation?
What is the role of histone modifications in epigenetic regulation?
What is the function of epigenetic writers, erasers, and readers?
What is the function of epigenetic writers, erasers, and readers?
What is the consequence of deregulation of histone modifications in diseases?
What is the consequence of deregulation of histone modifications in diseases?
What is the effect of environmental factors on epigenetic marks?
What is the effect of environmental factors on epigenetic marks?
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Study Notes
Nucleosome Structure
- Histone tails protrude out of the nucleosome, having a positively charged nature
- Histone tails play a crucial role in chromatin folding and co-factor recruitment
- N-terminal histone tails are the most accessible regions, possessing no specific structure
Histone Tail Modifications
- Histone tails are subjected to various post-translational modifications (m, methylation; a, acetylation; p, phosphorylation; u, ubiquitination)
- These modifications create sites for the recruitment of specific factors or modify existing sites to abolish previous interactions
- Chromatin must be first made "relaxed" to allow the access of cellular machineries to chromatin DNA
The Histone Code Hypothesis
- A core set of histone modifications define chromatin states
- 7 core histone modifications are associated with specific transcription events across the genome:
- H3K9Ac: active promoters
- H3K4me3: active promoters
- H3K4me1: enhancers and promoters
- H3K27Ac: enhancers and promoters
- H3K36me3: transcribed gene bodies
- H3K27me3: Polycomb-silenced promoters
- H3K9me3: Heterochromatin
Epigenetic Genome Annotation
- Chromatin accessibility and nucleosome position play a critical role in transcription factor binding and enhancer activity
- Densely populated nucleosomes are inaccessible and prevent the binding of transcription factors and cofactors
- Accessible, nucleosome-free regions are available for the binding of transcription factors
- Nucleosome positioning is a highly dynamic process, regulated by chromatin remodelers and pioneer transcription factors
Epigenomics
- Epigenomics help annotate regulatory elements
- Active enhancers are marked by H3K4me1 and H3K27ac, and are associated with the binding of transcription factors
Layers and Players in Epigenetic Regulation
- Modification of histone proteins involved in packaging DNA
- Methylation of DNA template
- Non-coding RNAs can influence both histone and DNA modifications
- Epigenetic layers: DNA methylation and histone modifications
- Both tagging systems are conserved and critical for development
- Tags are often deregulated in diseases (cancer, autoimmunity)
Epigenetic Writers, Erasers, and Readers
- Histones mediate chromatin compaction
- Histones are the template for PTM epigenetic modifications
- Histones are a group of basic proteins that associate with DNA and help the DNA to condense into chromatin
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