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Specific Epigenetic Modifications: DNA Methylation

This document summarizes various epigenetic mechanisms including DNA methylation, histone modifications, chromatin remodeling, and noncoding RNAs. It provides details on histone acetylation and methylation. Histone acetylation is correlated with gene activity and is regulated by histone acetyltransferases and deacetylases. Histone methylation does not alter charge but can correlate with transcriptional activity or inactivity, and occurs in mono, di, or tri-methylation. Modified histone tails act as docking sites for other proteins to influence chromatin structure.

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Richard S. Roxas
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29 views13 pages

Specific Epigenetic Modifications: DNA Methylation

This document summarizes various epigenetic mechanisms including DNA methylation, histone modifications, chromatin remodeling, and noncoding RNAs. It provides details on histone acetylation and methylation. Histone acetylation is correlated with gene activity and is regulated by histone acetyltransferases and deacetylases. Histone methylation does not alter charge but can correlate with transcriptional activity or inactivity, and occurs in mono, di, or tri-methylation. Modified histone tails act as docking sites for other proteins to influence chromatin structure.

Uploaded by

Richard S. Roxas
Copyright
© Attribution Non-Commercial (BY-NC)
We take content rights seriously. If you suspect this is your content, claim it here.
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Specific epigenetic modifications

DNA methylation
Methylation of 5 group of cytosines within CpG dinucleotides

Post-translational histone modifications


Methylation, ubiquitination, phosphorylation, sumoylation, acetylation of residues in the N-terminal tails of histones

Chromatin remodelling
ATP dependent chromatin remodelling complexes shift nucleosomes

Histone variants
Histones with varying stabilities or specialist domains that alter the function of the nucleosome

Noncoding RNAs
piRNAs and other siRNAs that can direct epigenetic machinery Long noncoding RNAs may direct epigenetic enzymes to sites in the genome

Histone Acetylation
Acetylation is correlated with gene activity (universally)
- reduces positive charge of histones, neutralises positive lysines, decreases attraction between histones (+) and DNA (-) - acts as docking site for other proteins, e.g. bromodomain proteins, that themselves open the chromatin (chromatin remodellers) or recruit them

Bromo ac

Histone Acetylation
Histones are acetylated by histone acetyltransferases, and acetyl groups are removed by histone deacetylases
HAT (KAT) 18 different genes in mouse HDACs 18 different genes in mouse

Histone Acetylation
Arguably not an epigenetic modification, rather just a chromatin modification
- due to the rapid acetylation/ deacetylation dynamics (circadian rhythm) - lack of mechanism for mitotic heritability

Histone Methylation

Histone methylation does not alter the charge of the histone Histone methylation can correlate either with transcriptional activity OR with inactivity Mono, di and tri-methylation exist

Histone Methylation
H3K9me transcriptionally inactive regions, usually constitutive heterochromatin, broadly over the whole gene Laid down by specific lysine methyltransferases, KMTs, with specific activity for H3K9 Removed by lysine demethylases, KDMs, with specific activity for H3K9me

Histone Methylation
H3K27me transcriptionally inactive regions, more commonly at facultative heterochromatin, broadly over the whole gene Laid down by specific lysine methyltransferases, KMTs (e.g. Ezh2, part of polycomb repressive complex 2, PRC2), with specificity for H3K27 Removed by lysine demethylases KDMs, with specificity for H3K27me3

How do histone modifications influence chromatin structure?


General rule: modified histone tails are read by other chromatin proteins; they act as docking sites for other epigenetic factors
- interacting proteins can have the ability to alter chromatin packaging (chromatin remodellers) - OR interacting proteins that then bring about other histone modifications

Modified histone tails act as docking sites for other chromatin proteins
Chromo, MBT PHD, Tudor

Bromo ac

me

14-3-3 P

Protein domains that bind Me, Ac or P at specific residues

Modified histone tails act as docking sites for other chromatin proteins
CHD1 HP1

me

H3

K
4

me

CBX2

K
9

Proteins that bind Me, Ac or P at specific residues

me

K
27

3 examples of chromodomain proteins


1. CHD1 ATP-dependent chromatin remodeller 2. HP1 - essential heterochromatin protein, can recruit DNMT1 3. CBX2 part of polycomb repressive complex that lays down H2AK119ub, another epigenetic mark

HP1 binds H3K9me3 HP1 can recruit DNMT HP1 can recruit HMT to maintain and spread the H3K9me3 mark DNMT can recruit HDAC

Example, incompletely understood regarding hierarchy

Summary

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