Coordinating DNA expression is an essential process for all living systems. The cell’s ability to execute the programs of life and death by regulating gene expression is controlled by complex interactions between signal transduction pathways, transcription factors, and modular protein regulatory complexes. The nucleosome is the fundamental unit of chromatin and is composed of 146 base pairs of DNA wrapped around an octamer of histone proteins (2 each of histone proteins H2A, H2B, H3, and H4).
Histones are modified in different ways, and one of the most studied set of modifications is the pattern of acetylation/deacetylation (see figure). Histone acetylation adds an acetyl moiety to the ε-amino group of the lysine tails on the histone protein. This modification is highly dynamic and is accomplished by a set of enzymes called histone acetyltransferases (HATs).
HATs are generally understood to alter chromatin structure by masking the positive charge of key lysine amino acid residues in the “tail” region of the histone proteins, thereby reducing the electrostatic interaction between the histone tail and the negatively charged DNA backbone. The process of histone acetylation creates an open chromatin structure that is associated with transcriptionally active DNA. HATs, including well-known family members p300/CBP, MOZ, and SRC, are transcriptional co-activators found in large multi-protein regulatory complexes that are recruited to promoter regions of target genes by transcription factors bound directly to the DNA.
The reverse process of acetyl group removal, or deacetylation, is accomplished by histone deacetylases (HDACs). The activity of HDAC enzymes is the reverse of HATs and creates transcriptionally quiescent regions of chromatin. The gene regulatory functions of HATs and HDACs are shown schematically in the figure below1.