Nature Genetics
19, 187 - 191 (1998)
doi:10.1038/561
Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription
Peter L. Jones1, Gert C. Jan Veenstra1, Paul A. Wade1, Danielle Vermaak1, Stefan U. Kass2, Nicoletta Landsberger3, John Strouboulis1
& Alan P. Wolffe11
Laboratory of Molecular Embryology, National Institute
of Child Health and Human Development, National Institute of Health,
Bethesda, Maryland 20892-5431, USA.
2
Department of Experimental Molecular Biology, Janssen
Research Foundation, Turnboutseweg 30, 2340 Bearse, Belgium. 3
Dipartimento Biologia Strutturale e Funzionale, Universita
di Varese, V. Ravasi 2, 2100 Varese, Italy.
Correspondence should be addressed to Alan P. Wolffe awlme@helix.nih.govCpG methylation in vertebrates correlates with alterations in chromatin
structure and gene silencing1,
2,
3,
4. Differences in DNA-methylation
status are associated with imprinting phenomena and carcinogenesis5,
6,
7,
8,
9,
10.
In Xenopus laevis oocytes, DNA methylation dominantly silences transcription
through the assembly of a repressive nucleosomal array5. Methylated
DNA assembled into chromatin binds the transcriptional repressor MeCP2 which
cofractionates with Sin3 and histone deacetylase. Silencing conferred by MeCP2
and methylated DNA can be relieved by inhibition of histone deacetylase, facilitating
the remodelling of chromatin and transcriptional activation. These results
establish a direct causal relationship between DNA methylation-dependent transcriptional
silencing and the modification of chromatin.
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