Acetylated histones transcriptional activity

Hebbes, T., Thorne, A.W., and Crane-Robinson, C. (1988) A direct link between core histone acetylation and transcriptionally active chromatin. EMBO J. 7, 1395-1403. 

Besides counteracting the cell-cycle arrest phenotype of trichostatin A, the ITSAs counteract trichostatin-induced histone acetylation and transcriptional activation. Some of these ITSAs are active as suppressors of trichostatin A in zebrafish and yeast suggesting they target an evolutionarily conserved component of chromatin remodeling. As such, suppressors of HDAC inhibitors, such as the ITSAs, may prove to be valuable probes of many biological processes involving protein acetylation. 

Wade PA, Wolffe AP (1997) Chromat/w Histone acetyltransferases in control. Curr Biol 7 R82-R84 Keirmaier A, Eilers M (1997) Transcriptional control Calling in histone deacetylase. Curr Biol 7 R505-R507 Davie JR (1997) Nuclear matrix, dynamic histone acetylation and transcriptionally active chromatin. Mol Biol Rep 24 197-207... 

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 core unit of the chromatin, the nucleosome, consists of histones arranged as an octamer consisting of a (H3/ H4)2-tetramer complexed with two histone H2A/H2B dimers. Accessibility to DNA-binding proteins (for replication, repair, or transcription) is achieved by posttranslational modifications of the amino-termini of the histones, the histone tails phosphorylation, acetylation, methylation, ubiquitination, and sumoyla-tion. Especially acetylation of histone tails has been linked to transcriptional activation, leading to weakened interaction of the core complexes with DNA and subsequently to decondensation of chromatin. In contrast, deacetylation leads to transcriptional repression. As mentioned above, transcriptional coactivators either possess HAT activity or recruit HATs. HDACs in turn act as corepressors. 

The structure of the chromatin and their state of acetylation are important at the moment of initiating the gene transcription. Indeed, some of the transcription factors recruited by the receptor dimer have histone-acetyltransferase activity that permits the gene transcription after diminishing the condensation of the chromatin (Gruber et al. 2002 Nilsson et al. 2001 Vigushin et al. 2002). 

One of the most-studied covalent modifications is the acetylation of the lysine residues of histone tails. The acetylation state of lysines of nucleosomal histones modulates chromatin structure and regulates gene transcriptional activity. The balance of lysine acetylation is controlled by the antagonistic action of two enzyme families histone deacetylases (HDACs) and histone acetyltransferases (HATs). In humans there are essentially three main HDAC subclasses [6]. 

H2A Barr body-deficient (Bbd) is an evolutionary relatively young histone variant sharing only about 48% amino acid sequence similarity to H2A. This histone variant appears to be specific for mammals (Chadwick and Willard 2001). As indicated by the name, the transcriptionally inactive and highly condensed X chromosome in female mammals (also known as Barr body ) is depleted for H2A , while this variant is detectable in autosomes and the active sex chromosomes. This observation suggested that H2A is linked to transcriptionally active euchromatin. H2A cofractionates in sedimentation centrifugation with hyper-acetylated histone H4, further corroborating that it associates with transcriptionally active euchromatin. 

Figure 2. Histone chaperones facilitate favorable chromatin dynamics during transcriptional activation Transcriptional competence of chromatin template is achieved by die replacement of histone variants and finally removal of histones. Histone chaperone may help in bodi die process in a replication independent manner. Acetylation of histone and also die chaperone may assist in diis process. Recent evidence suggest that NPMl may participate in these events globally or gene specific manner. (See Colour Plate 11.)...

Figure 1. Mechanistic effect of acetylation/deacetylation of histones and nonhistones on chromatin stracture.(a) Acetylation of non-histone proteins results in transcriptional activation (b) Acetylation of ORCl by HBOl is important for replication, (c) Acetylation of newly synthesized...

Acetylation of p53, E2F and many other proteins not only activates their transcriptional activities but also half-life (Li et al, 2002 Martlnez-Balbas et al, 2000). Apart from DNA binding, and protein half-life, acetylation also plays pivotal role in protein-protein interactions thereby cellular processes involved. However, the acetylation of pRb regulates the specific interaction with E2F-1 (Markham et al, 2006). E2F activity is negatively regulated by its interaction with pRb, which recruits histone decetylase complexes and probably lead to the deacetylation of E2F. 

Bariev NA, Liu L, Chehab NH, Mansfield K, Harris KG, Halazonetis TD, Berger SL (2001) Acetylation of p53 activates transcription through recruitment of coactivators/histone acetyltransferases. Mol Cell 8 1243-1254... 

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