Histone binding domain

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. 

Figure 3. Representative linker histone variants from human (Homo sapiens H.s.), and yeast (Saccha-romyces cerevisiae S.c.). The globular domain indicates the winged helix DNA binding domain that is common for all linker histones. Hlc is a typical somatic linker histone common for most cells. H° is expressed in all somatic cells, but is more abundant in terminally differentiated tissues. Hlfoo is an oocyte-specific linker histone. The structure of S. cerevisiae Hholp with two globular domains is a notable deviation...

Zeng L, Zhou MM (2002) Bromodomain an acetyl-lysine binding domain. EEBS letters 513 124-128 Zhang Y, Reinberg D (2001) Transcription regulation by histone methylation interplay between different covalent modifications of the core histone tails. Genes Dev 15 2343-2360... 

Although chemically modifying DNA have distinctive implications for chromatin transitions and fiber structure in the presence of HI [250], in vivo these effects appear to work in concert with chromosomal proteins. 5 -Methylcytosines are specifically bound by members of the MBD (methyl-CpG-binding-domain) family, such as MeCP2 (Methyl-Cytosine binding Protein 2) and MBDl. These proteins have been shown to interact with HDACs and provide a casual link between DNA methylation, histone deacetylation and transcriptional repression [251-253]. 

The solution structure of the methyl-CpG binding domain of human MBDl complexed with a methylated oligonucleotide has been recently presented [164], The structure indicates how MBD may access nucleosomal DNA without encountering steric hindrance from the histone octamer. 

Fig. 8. Proposed models that link histone methylation to DNA methylation (for details see Section 5.2). Methylated cytosines attract histone methyltransferases that contain a methyl-binding domain or a methyl-CpG binding protein (MeCP2) that recruits histone methylase activities these introduce methyl groups into the histone tails. The binding of chromodomain HPl proteins to H3 tails methylated at lysine 9 generates a secondary layer of repressive chromatin structure, (b) In a reverse scenario, methylated histone tails attract chromodomain-binding proteins, which in turn recruit Dmnts to methylate adjacent DNA sequences.

Holbert, M.A., Sikorski, T., Carten, J., Snowfiack, D., Hodawadekar, S. and Marmorstein, R. (2007) The human monocytic leukemia zinc finger histone acetyltransferase domain contains DNA-binding activity implicated in chromatin targeting. The Journal of Biological Chemistry, 282 (50), 36603-36613. 

The effects of DNA-binding transactivators on Pol II are mediated by coactivator protein complexes such as TFIID or mediator. The modular structures of the transactivators have distinct activation and DNA-binding domains. Other protein complexes, including histone acetyltransferases such as GCN5-ADA2-ADA3 and ATP-dependent complexes such as SWI/SNF and NURF, reversibly remodel chromatin structure. 

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