New role for histone deacetylase 9 in atherosclerosis and inflammation.

Abstract

Epigenetic regulation of gene expression is mediated by DNA methylation as well as by modification of nucleosome structure and cofactor recruitment through histone modifications. Specific methylation and acetylation of histone lysine residues, which comprise the so-called histone code, are marks of different chromatin states related to the expression of neighboring genes and the activity of promoters and enhancers. Histone acetylation and methylation, along with their role in regulating transcription has been known since the 1960s. The enzymes that make these modifications can be thought of as chromosome writers, whereas the enzymes that remove these marks can be referred to as chromosome erasers. Another set of proteins sense these marks and alter gene expression, which can be termed chromosome readers. Histone acetylation is performed by members of the histone acetyltransferase gene family, which use acetyl-CoA as a cofactor to modify specific e-amino group of lysine residues on different histone proteins. This modification eliminates lysine’s positive charge and reduces the affinity of the histone for DNA, which can result in a more relaxed chromatin conformation that can facilitate the recruitment of DNA binding effector proteins. Thus, histone acetylation is most often associated with increased transcriptional activity, and in the most extreme case, acetylation of lysine 16 on histone H4 (H4K16ac) is involved in the switch from inactive heterochromatin to euchromatin.1 Histone acetylation is reversible, allowing for environmental and developmental gene regulation, usually repression; and this process is performed by members of the …