The MTA family proteins as novel histone H3 binding proteins

In this study, we show among several class I HDAC-containing corepressor complexes only NURD exhibits a substantial H3 tail-binding activity in vitro. We present the evidence that the MTA family proteins within the NURD complex interact directly with H3 tail. Extensive in vitro binding assays mapped the H3 tail-binding domain to the C-terminal region of MTA1 and MTA2. Significantly, although the MTA1 and MTA2 mutant proteins with deletion of the C-terminal H3 tail binding domain were assembled into the endogenous NURD complex when expressed in mammalian cells, the resulting NURD complexes were deficient in binding H3 tail in vitro, indicating that the MTA family proteins are required for the observed specific binding of H3 tail peptide by NURD in vitro. However, chromatin fractionation experiments show that the NURD complexes with impaired MTA1/2-H3 tail binding activity remained to be associated with chromatin in cells.Together our study reveals a novel histone H3-binding activity for the MTA family proteins and provides evidence that the MTA family proteins mediate the in vitro specific binding of H3 tail peptide by NURD complex. However, multiple mechanisms are likely to contribute to the chromatin association of NURD complex in cells. Our finding also raises the possibility that the MTA family proteins may exert their diverse biological functions at least in part through their direct interaction with H3 tail.Histone lysine acetylation plays a central role in the epigenetic regulation of gene expression [1-3]. The levels of histone acetylation in eukaryotic cells are governed by the opposing activities of histone acetyltransferases(HATs) and histone deacetylases (HDACs) [3]. The mammalian genome encodes a significant number of HDACs, among them are the abundantly and ubiquitously expressed class I HDACs that include HDAC1, HDAC2 and HDAC3 [3]. The class I HDACs are mainly found in stable multi-subunit complexes with co-repressor proteins like Sin3A [4,5], CoREST