Histone tails

An enzyme activity ascribed to many coactivators, which transfers acetyl groups to lysine residues of histone tails of the nucleosomes and thereby facilitate their disruption and the opening of the chromatin. 

In addition protein domains have been identified which bind to modified histone tails. The so-called bromodomains bind to acetylated histone tail, but have little or no affinity to unmodified tails. Further known binding domains include chromodomains and SANT domains which possess preferential binding to methylated and unmodified tails. 

Enzyme activity ascribed to corepressors, which is the removal of acetyl groups from lysine residues of histone tails. Thereby the assembly of nucleosomes is maintained, which leads to a dense, transcriptional inactive chromatin structure. 

Histone tails are the N-terminal regions of histones which reach outside the nucleosomes. They are not essential for the formation in of nucleosomes but are required for the formation of higher-order chromatin structures. The histone tails are also known to be heavily posttranslationally modified by acetylation, phosphorylation, methylation, etc. and are important for the regulation of gene activity. 

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. 

Histone Acetylation Histone Deacetylases Histone Methylation Histone Phosphorylation Histone Tails Hrv... 

In addition to histone deacetylation, histone lysine methylation can also lead to gene silencing which is not blocked by the HDAC inhibitors [6, 51], Several lines of evidence have suggested a connection between cancer and histone lysine methyltrans-ferases (HKMTs) [52], HKMTs catalyze the transfer of methyl group(s) from the cofactor. S -adenosyI-methionine (AdoMet) to some specific lysine residues in the N-terminal histone tails [53, 54], With one exception of Dotl [55], all known HKMTs contain the SET domain which represents a novel structural fold [53, 56], Among SET-domain HKMTs, SET7/9 is one of the best characterized experimentally. It is a... 

The dynamic and differential methylation of lysine residues in histone tails plays a central role in the creation of the histone code and the regulation of chromatin structure and function that the code implies [12]. For example, different lysine methylation marks (KMe) are... 

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]. 

Figure 1. Hierarchical model of chromosome structure, (a) In interphase cells, DNA is packed in a nucleus as forming nucleosome and chromatin, (b) DNA forms nucleosome structure together with core histone octamer, which is then folded up into 30nm fiber with a help of linker histone HI. This 30 nm fiber is further folded into 80 nm fiber and 300 nm loop structures in a nucleus. In mitosis, chromosome is highly condensed. Proteins which are involved in each folding step are indicated above and non-protein factors are indicated below, (c) The amino acid sequences of histone tails (H2A, H2B, H3 and H4) are shown to indicate acetylation, methylation and phosphorylation sites. (See Colour Plate 1.)...

In addition to the role for the nucleosome-nucleosome interactions, the histone tails are known as the region that undergoes post-transcriptional modifications, such as acetylation, phosphorylation, and methylation (Fig. Ic) (Peterson and Laniel, 2004). These modifications trigger the formation of euchromatin (acetylation), heterochromatin (methylation), or metaphase chromosome (phosphorylation). The details of these modifications will be described in chapters 8-11. 

Acetylation of the histone tails correlates with the activities of genes (Kimura et al., 2005). However, the detailed analyses of the acetylation on the individual lysine residue have revealed that the relationship between the acetylation and the chromatin-compaction is not simple. There are 1-6 lysine residues in each histone subunit, that could be acetylated the Lys of H2A, Lys, Lys, Lys, and Lys ° ofH2B, Lys , Lys , Lys, Lys, Lys, andLys of H3, and Lys, Lys, Lys, and Lys of H4. In mammal, more than ten HATs (7/istone Acetyl Transferases) have been identified, each of which acetylates a specific lysine residue. Acetylation frequently occurs in euchromatin regions, and some in heterochromatin regions. For example, the acetylation of Lys of H4 leads to a telomeric silencing (Kelly et al., 2000). In Drosophila, Lys of H4 is acetylated specifically in the... 

Zheng C, Hayes JJ (2003) Structures and interactions of the core histone tail domains. Biopolymers 68 539-546... 

Cross-linkers, Chromatin condensation. Histone tails, Nucleosome phasing... 

Epigenetic is a term used to describe a state of gene expression that is mitotically and meiotically inherited without any change in the sequence of DNA. Epigenetic mechanisms are mainly of two classes (1) the DNA may be modified by the covalent attachment of a moiety that is then perpetuated. (2) a self-perpetuating protein state may be established (Zelent et al, 2004). The two most studied epigenetic phenomena are DNA methylation and histone tail modifications (Mai et ai, 2005). 

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