The histone acetylation link

The past few years witnessed some important developments that established a molecular link between CpG methylation and the status of histone acetylation. It was shown that the methyl-binding protein MeCp2 contains a transcriptional repressor domain that interacts directly with the multiprotein corepressor complex mSin3A [84,86]. Antibodies against MeCP2 coprecipitated mSin3A, HDACl and HDAC2, and the deacetylase inhibitor trichostatin A (TSA) relieved the repression. 

Finally, the deacetylation of histones in methylated gene regions may be selective with respect to the histone affected. Chromatin immunoprecipitation analysis of the histone acetylation status of proviral sequences targeted to defined genome loci in MEL cells showed that the in vitro methylated proviral sequences that were transcriptionally silent in vivo, were hypoacetylated only with respect to histone H3 in contrast, the acetylation status of histone H4 was comparable on the methylated and unmethylated provirus [78]. Moreover, the H3 acetylation status correlated closely with the location of methylated CpGs along the proviral sequence. 

As mentioned earlier, MeCP2 is not the only protein that associates with HD AC activities. Both MBD2 and MBDl repress transcription in histone deacetylation-dependent manner. Interestingly, MBD2 was found associated not only with class I histone deacetylases (HDACl and 2) from the Mi2/NuRD corepressor complex but also with class II histone deacetylases in the silencing mediator of retinoic and thyroid receptor (SMRT)/HDAC 5,7 complex [137]. 

3 Inhibition of histone acetyiation prevents active DNA demethyiation and transcription 

Collectively, the results of these studies suggest a dominant role for DNA methylation, which dictates the acetylation status of the histones, and thereby, chromatin structure (Fig. 5c). The cells jealously preserve and inherit DNA methylation patterns, and respectively chromatin conformation, through mitosis. 

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