Histone acetylation occurs on histones H2A, H2B, H3, and H4, but it is best described in brain on H3 where it can occur on the N-terminal tails at lysines 9, 14, 18, and 23 and on H4 at lysines 5, 8, 12, and 16 [24]. Histone acetylation is thought to affect the activity of a gene through two main mechanisms. First, acetylation of lysine residues reduces their positive charge and thus their electrostatic attraction to the negatively charged backbone of DNA. This reduced electrostatic attraction is thought to result in a “looser” chromatin structure allowing greater access of transcriptional activators to the underlying gene. Second, acetylated histones serve as a substrate for bromodomain-containing proteins [25]. An example of such a protein is TAFII250, which contains two bromodomains that recognize polyacetylated histone H4 [26]. TAFII250 along with the TATA-binding protein (TBP), recruit other components of the transcriptional machinery, including RNA polymerase, which ultimately transcribes the gene [27]. As would be predicted from its biochemical role, genome-wide promoter analyses in a variety of cells, tissues, and species have identified strong correlations between
