Histone acetyl transferase

Clock gene and transcription factor with histone acetyl-transferase (HAT) activity that (in complex with BMAL1) constitutes a positive limb of molecular circadian oscillators. 

The exact role of individual histone acetylations will have to be determined in the context of other modifications and the number of lysine residues effected. However, the general importance of histone acetylation as a regulator for chromatin activity is undisputed. This leads to the intriguing possibility to develop drugs that target histone acetylation for therapeutic purposes. The primary targets for drug development are the histone acetyl transferases (HATs) and the histone deacetylases (HDACs) which introduce and remove histone acetylations [2, 3]. 

TBP-RNA polymerase) (ii) they are potent histone acetyl transferases inducing chromatin remodeling (loosening). 

Legube G, Linares LK, Tyteca S, Caron C, Scheffner M, Chevillard-Briet M, Trouche D (2004) Role of the histone acetyl transferase Tip60 in the p53 pathway. J Biol Chem 279 44825 4833 Linggi BE, Brandt SJ, Sun ZW, Hiebert SW (2005) Translating the histone code into leukemia. J Cell Biochem 96 938-950... 

Utley RT, Lacoste N, Jobin-Robitaille O, Allard S, Cote J (2005) Regulation of NuA4 histone acetyl-transferase activity in transcription and DNA repair by phosphorylation of histone H4. Mol Cell Biol 25(18) 8179-8190... 

Chun TW, Engel D, Mizell SB, Ehler LA, Fauci AS (1998) Induction of HIV-1 rephcation in latently infected CD4-t T cells using a combination of cytokines. J Exp Med 188 83-91 Col E, Caron C, Seigneurin-Berny D, Gracia J, Favier A, Khochbin S, (2001) The histone acetyl-transferase, hGCN5, interacts with and acetylates the HIV transactivator. Tat. J Biol Chem... 

Vandel, L. and Trouche, D. (2000) Physical association between the histone acetyl transferase CBP and a histone methyl transferase. EMBO Rep. 2, 21-26. 

Biochemistry of the Histone Deacetylases and Histone Acetyl Transferases 296... 

The family of HDAC enzymes has been named after their first substrate identified, i.e., the nuclear histone proteins. Histone proteins (H2A, H2B, H3 and H4) form an octamer complex, around which the DNA helix is wrapped in order to establish a condensed chromatin structure. The acetylation status of histones is in a dynamic equilibrium governed by histone acetyl transferases (HATs), which acetylate and HDACs which are responsible for the deacetylation of histone tails (Fig. 1). Inhibition of the HDAC enzyme promotes the acetylation of nucleosome histone tails, favoring a more transcriptionally competent chromatin structure, which in turn leads to altered expression of genes involved in cellular processes such as cell prohferation, apoptosis and differentiation. Inhibition of HDAC activity results in the activation of only a limited set of pre-programmed genes microarray experiments have shown that 2% of all genes are activated by structmally different HDAC inhibitors [1-5]. In recent years, a growing number of additional nonhistone HDAC substrates have been identified, which will be discussed in more detail below. 

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. 

Roth SY, Denu JM, Allis CD. Histone acetyl transferases. Annu. 

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