Histone-modifying enzymes
Type of enzymes / From Wikipedia, the free encyclopedia
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Histone-modifying enzymes are enzymes involved in the modification of histone substrates after protein translation and affect cellular processes including gene expression.[1][2] To safely store the eukaryotic genome, DNA is wrapped around four core histone proteins (H3, H4, H2A, H2B), which then join to form nucleosomes. These nucleosomes further fold together into highly condensed chromatin, which renders the organism's genetic material far less accessible to the factors required for gene transcription, DNA replication, recombination and repair.[3][4] Subsequently, eukaryotic organisms have developed intricate mechanisms to overcome this repressive barrier imposed by the chromatin through histone modification, a type of post-translational modification which typically involves covalently attaching certain groups to histone residues. Once added to the histone, these groups (directly or indirectly) elicit either a loose and open histone conformation, euchromatin, or a tight and closed histone conformation, heterochromatin. Euchromatin marks active transcription and gene expression, as the light packing of histones in this way allows entry for proteins involved in the transcription process. As such, the tightly packed heterochromatin marks the absence of current gene expression.[4]
While there exist several distinct post-translational modifications for histones, the four most common histone modifications include acetylation,[5] methylation,[6] phosphorylation[7] and ubiquitination.[8] Histone-modifying enzymes that induce a modification (e.g., add a functional group) are dubbed writers, while enzymes that revert modifications are dubbed erasers. Furthermore, there are many uncommon histone modifications including O-GlcNAcylation,[9] sumoylation,[10] ADP-ribosylation,[11] citrullination[12][13][14] and proline isomerization.[15] For a detailed example of histone modifications in transcription regulation see RNA polymerase control by chromatin structure and table "Examples of histone modifications in transcriptional regulation".