In the intact cell, DNA closely associates with histones and other nuclear proteins to form chromatin. The remodeling of chromatin is believed to be a critical component of transcriptional regulation, and a major source of this remodeling is brought about by the acetylation of nucleosomal histones. Acetylation of lysine residues in the amino terminal tail domain of histone results in an allosteric change in the nucleosomal conformation and an increased accessibility to transcription factors by DNA. Conversely, the deacetylation of histones is associated with transcriptional silencing. Several mammalian proteins have been identified as nuclear histone acetylases, including GCN5, PCAF (for p300/CBP-associated factor), p300/CBP and the TFIID subunit TAF II p250. Mammalian HDAC1 (also designated HD1) and HDAC2 (also designated mammalian RPD3), both of which are related to the yeast transcriptional regulator Rpd3p, have been identified as histone deacetylases.
