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Generic Enzyme
Generic kinase
Protein kinase
Lipid kinase
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RAS - superfamily
G beta/gamma
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Cell membrane glycoprotein
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Predicted metabolite or user's structure
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Normal process
Pathological process
Covalent modifications
Transcription regulation
MicroRNA binding
Influence on expression
Unspecified interactions
Pharmacological effect
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Complex subunit
Similarity reaction
A complex or a group
Organism specific object

Histone modification

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Histone modification

Histone modification

Histones participate in modulation of gene expression by regulation ofchromatin condensation. Different modifications of histone molecules are epigeneticregulators of chromatin. The histone modifications influence higher-order chromatinstructure by affecting contacts between different histones and between histones and DNA.Common histone modifications include acetylation, phosphorylation, methylation andubiquitination [1], [2].

Trimethylation of Histone H3 at lysine 4 (H3K4), lysine 36 (H3K36), or lysine79 (H3K79) results in an open chromatin configuration and is therefore characteristic ofeuchromatin. Condensed heterochromatin is enriched in trimethylation of Histone H3lysine 9 (H3K9), lysine 27 (H3K27), and Histone H4 lysine 20 (H4K20), whilesilencing of euchromatin involves the recruitment of specific lysine 9 histonemethyltransferases [3], [2]. Methylated H3K9 provides a bindingsite for the chromodomain-containing Chromobox homolog ( HP1 ), which inducestranscriptional repression and heterochromatinization [1], [2].Coactivator-associated arginine methyltransferase 1 ( CARM1 ) possessesarginine-specific, Histone H3-selective methyltransferase activity and participates inligand-dependent transcriptional activation [4].

The Histone demethylase amine oxidase domain 2 ( LSD1 (BHC110) ) is responsiblefor H3K4 demethylation, which leads to transcriptional inactivation [2].

Euchromatin is also characterized by a high level of histone acetylation,which is mediated by histone acetyl transferases. Conversely, histone deacetylases havethe ability to remove this epigenetic mark, which leads to transcriptional repression[5], [2]. In the most studied species from, the mainacetylation sites of Histone H3 are lysines 9, 14, 18 and 23, as well as lysines5, 8, 12 and 16 that are also acetylated during specific cellular processes in thefunctionally redundant tail of H3's nucleosomal partner, Histone H4 [4].

H3 phosphorylation at serine 10 is directly correlated with the induction ofimmediate-early genes and, possibly in conjunction with phosphorylation at serine, isrequired for proper segregation and condensation of chromosomes during mitosis andmeiosis [4]. High-mobility group nucleosome binding domain 1 ( HMG14) binds the nucleosomal core particles and directly modulate phosphorylation ofnucleosomal H3 by hindering the exposure of the Histone H3 N-terminal domain to Ribosomalprotein S6 kinase 90kDa polypeptide 5 ( MSK1 ) [6]. AlsoHigh-mobility group nucleosomal binding domain 2 ( HMGN2 ) can binds nucleosomes[7]. Others HMG, for example High-mobility group 20B ( HMG20B) can bind DNA in a sequence-specific or non-sequence-specific mode to induce DNAbending, and regulate chromatin function and gene expression [8].

Histones can also be modified through ubiquitination. Histone H2A was the firstprotein identified to be ubiquitinated at lysine 119. Like Histone H2A, HistoneH2B is ubiquitinated at lysine 120 in human. Ubiquitination and deubiquitination ofhistones, as well as combination of different histone modifications, play important rolesin transcriptional regulation. However, the exact role is still elusive [9].