MethylCpGBinding Proteins Histone Deacetylation and Chromatin Remodeling

In 1998, Nan et al.57 and Jones et al.58 reported independently that MeCP2 resided in a complex with several histone deacetylases (HDACs). The complex also contained Sin3A, a corepressor in other deacetylation-dependent silencing processes, plus several additional unidentified proteins. Both laboratories demonstrated that transcriptional silencing could be reversed by trichostatin A, a specific inhibitor of histone deacetylases. Additionally, both obtained evidence that histone deacetylation was guided to specific chromatin domains by genomic methylation patterns, and that transcriptional silencing relied on histone deace-tylation. Earlier contributions of Vincent Allfrey and of Vernon Ingram, whose laboratories were both engaged in studying biochemical events relevant to gene regulation, should also be acknowledged in the context of transcriptio-nal regulation. Both of these investigators had proposed several years earlier that acetylation (Allfrey) and methylation (Ingram) of histones were linked to gene regulation59 and that inhibition of histone deacetylation could alter cellular differentiation.60

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