Transcriptional Activity and Histone Acetylation

Recent studies have shown that the acetylation or deacetylation of the histones of the nucleosome plays an important role in the regulation of transcriptional activity. Acetylation of the histones (review Hassig and Schreiber, 1997) is a postranslational modification which is usually performed on lysine residues at the N-terminus and requires specific enzymes,the histone acetyl transferases (HATs). Removal of the acetyl group also requires specific enzymes, the histone deacetylases (HDAC). Most importantly, the acetylation of histones is accompanied by a loss of postive charges which is thought to have a profound influence on the nucleosome structure and on the strength of DNA-binding. 

In many, although not aU, cases, the histone acetylation is correlated with a stimulation of transcriptional activity. HAT activity is found in proteins associated with the transcription apparatus or identified as coactivators. Examples are, among others, members 

The mechanism of transcriptional activation via histone acetylation remains speculative. Two models, which are not mutually exclusive, are currently discussed  

The amino terminal tads of the four core histones contain lysines that are acetylated by HATs and deacetylated by HDACs. The histone octamer (H2A, H2B, H3, H4)2 is represented as a cylinder wrapped by DNA. It is thought that neutrahzation of the positive charges on the histone tads results in alterations of the nucleosome structure that may lead to a higher mobdity of the nucleosome and/or an improved accessibdity of the bound DNA, with accompanying changes in chromatin structure, chromatin hierarchy and transcription. In most, but not ad cases, deacetylation correlates with the repressed state and acetylation correlates with the transcriptionady active state. 

The amino termind of the histones are indicated by a circled N charged lysines are represented by + and acetylated lysines are indicated by Ac. Only the hyper- and hypoacetylated states are depicted. 

The HAT enzymes can be grouped by cellular localization into two classes. Typ A H ATs are localized in the nuclei and acetylate nuclear proteins, while, in contrast, type B HATs are found in the cytoplasm and probably acetylate newly synthesized histones. 

A large part of the HAT activity functions in a gene-specific manner via specific interactions between transcription activators and the HAT complexes. We now know of numerous examples of transcription activators that target HAT activity to specific genes. A HAT enzyme recruited by many activators is p300/CBP, which is found as part of the PCAF complex. Examples of transcription activators that recruit HAT activity are 

As already mentioned, the HAT enzymes are found in most cases as part of the coactivator complexes required for the function of these activators. 

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