Protein modules that manipulate histone tails for chromatin regulation

Abstract

Chromatin is composed of nucleosomes, which consist of DNA and histone proteins. The histone amino terminus has a 'tail' region that is highly conserved between species and consists of protein modules that are responsible for post-translational modification of histones. Many histone modifications take place in the form of acetylation, methylation or phosphorylation, and have been correlated with nuclear activities such as replication, chromatin assembly and transcription. It is thought that modification of histones is a sequential or combinatorial process such that a 'histone code' materializes which promotes transcriptional events downstream. Histone acetylation/deacetylation is the most studied histone modification activity. It is correlated with transcriptional activation/repression. The enzymes that mediate this process are histone acetyltransferases (HATs) and histone deacetylases (HDACs). Bromodomain and kinase domain modules can act as transcriptional coactivators by aiding the process to proceed. There are distinct functional links between HATs/HDACs and these modules. Gene silencing occurs during the formation of higher-order heterochromatin through histone methylation. This process is aided by SET domains and chromodomains. Other conserved protein modules involved in histone modification are also known, although their biochemical functions are as yet poorly defined. Of those modules that have been studied extensively, it is still not entirely clear what the function of these modules is or in what sequence they interact with histone tails to coordinate and regulate gene expression. Futher studies will concentrate on these issues.