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Specific epigenetic modificationsDNA 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 machineryLong noncoding RNAs may direct epigenetic enzymes to sites in the genome

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Different variants exist for histones H2A, H3 and H1

Each variant has specific properties that differ from the canonical

histones, useful for different functions e.g.

- Increased stability vs decreased stability- Amino acids that can be modified such as Serine (can be

phosphorylated), not found in canonical histones

- Others we dont yet understand

Histone variants

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- How are histone variants deposited?- Using ATP-dependent chromatin remodelling proteins- Can be replication dependent or independent

i.e. does or doesnt rely on cell division

Histone variant deposition

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Centromeric histone variants e.g. CENP-A (different names in otherspecies)

- Centromere specific (centromere is the primary constriction of ametaphase chromosome)

centromere

Histone variants variant H3

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H2A.X involved in DNA repair

- Universal histone variant, highly conserved- C terminal motif differs from canonical H3- Has Serine at position 139, which can be phosphorylated- H2A.X-ph, called -H2A.X, localised in double strand breaks

(DSB), and is involved in DNA repair

Histone variants variant H2A.X

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- S139 phosphorylated by kinases at DSB- -H2A.X recruits DNA repair proteins, including epigenetic factors that alter

chromatin state at DSB

- Phosphatase cleaves phosphate group after repair is complete

Histone variants variant H2A.X

DNA stained blue-H2A.X green, marks DSBpost irradiation

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Histone variants variant macroH2A

MacroH2A inactive X chromosome

- Found only in vertebrates- Contains large 200 amino acid C terminal macro domain- Enriched on the inactive X chromosome, chromosome made up of

facultative heterochromatin

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Histone variants summary

Many different variants, 3 we discussed Variants possess particular domains or amino acids that enable

specific features

Histone variants are known that are involved in structuralaspects of the chromosome, DNA repair and transcriptional

silencing or activation

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Acknowledgements

Chromosome (http://commons.wikimedia.org/wiki/File:Chromosome-upright.png)By Magnus Manske, modifications 'upright chromosome' by User:Dietzel65

(Nupedia, then en.wikipedia) [CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/)], via Wikimedia Commons

YH2AX Foci in a nucleus of a mouse cell(http://commons.wikimedia.org/wiki/File%3AYH2AX_Foci_in_a_nucleus_of_a_mouse_cell.tif) by By Newheavyions

(Own work) [CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0)], via

Wikimedia Commons

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