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Histone H4 acetylation at K16 residue and mitochondrial activity in neuronal cells
Author(s) -
Dmitriev Ruslan I,
Zhdanov Alexander V,
Papkovsky Dmitri B
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.565.4
Subject(s) - acetylation , histone , biology , microbiology and biotechnology , gene expression , regulation of gene expression , histone h4 , calreticulin , biochemistry , mitochondrion , epigenetics , gene , endoplasmic reticulum
The role of acetylation of histone H4 tail at residue K16 (H4K16Ac) in epigenetic regulation is widely recognized as the mark of nucleosome de‐compactization and activation of gene expression. The enzymes responsible for this modification are histone acetyl transferases (HATs) which use acetyl‐CoA (ACA) as a substrate. Recently it has been shown that mitochondria can supply ~50% of the total pool of ACA for this modification suggesting their role in the regulation of H4K16Ac. We hypothesized that this may occur under certain stress conditions such as ischemia‐reperfusion. Neuronal‐like PC12 cells were exposed to oxygen‐glucose deprivation (OGD) for different time intervals. A dramatic decrease in H4K16Ac has been found during the OGD, which could be reversed to the original levels by reperfusion. On the other hand, gene expression analysis did not show any changes in the expression of known H4K16Ac targets, namely, the UCP2, calreticulin and HIP1. The activity of HAT MYST1 (KAT8) may involve the acetylation of p53 with following activation of BAX and PUMA genes; however we failed to demonstrate any changes in their expression in samples exposed to OGD. This concludes that the decrease of H4K16Ac and possible acetylation of other proteins during ischemia‐reperfusion treatment may not related to regulation of UCP2, calreticulin and HIP2 genes and needs further investigation. Supported by SFI.