18 Questions
What is the primary function of histone tail modifications?
To create binding sites for transcription factors
What is the correlation between chromatin packing and gene expression levels?
Loosely packed chromatin is associated with high gene expression
What is the term used to describe the process of histone modifications regulating gene expression?
Epigenetic regulation
Why must chromatin be made 'relaxed' before cellular machineries can access chromatin DNA?
To allow access to chromatin DNA
What is the primary role of histone N-terminal tails?
To recruit transcription factors
What was the prevailing view of histones before the discovery of histone modifications?
As structural proteins for chromatin compaction
What histone modification is associated with transcribed gene bodies?
H3K36me3
Which histone modification is a mark of Polycomb-silenced promoters?
H3K27me3
What is the role of chromatin remodelers in the regulation of gene expression?
To regulate the transition from closed inactive to active chromatin
Which histone modification is associated with active promoters?
H3K9Ac
What is the result of densely populated nucleosomes on transcription factor binding?
They prevent transcription factor binding
What is the characteristic of active enhancers?
They are marked by H3K4me1 and H3K27Ac
What is the function of histone proteins in epigenetic regulation?
To help DNA condense into chromatin
What is the effect of DNA methylation on gene expression?
It silences gene expression
What is the role of histone modifications in epigenetic regulation?
They can either silence or activate gene expression depending on the tag
What is the function of epigenetic writers, erasers, and readers?
To add, remove, or recognize epigenetic marks on histones
What is the consequence of deregulation of histone modifications in diseases?
It leads to both cancer and autoimmunity
What is the effect of environmental factors on epigenetic marks?
They can influence epigenetic marks
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
Learn about the histone code nomenclature and how specific histone modifications are associated with transcription events across the genome. Understand the role of chromatin accessibility and nucleosome position in epigenetic genome annotation.
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