Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription.
CpG methylation in vertebrates correlates with alterations in chromatin structure and gene silencing. Differences in DNA-methylation status are associated with imprinting phenomena and carcinogenesis. In Xenopus laevis oocytes, DNA methylation dominantly silences transcription through the assembly of a repressive nucleosomal array. 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.
Jones
P L
PL
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institute of Health, Bethesda, Maryland 20892-5431, USA.
Veenstra
G J
GJ
Wade
P A
PA
Vermaak
D
D
Kass
S U
SU
Landsberger
N
N
Strouboulis
J
J
Wolffe
A P
AP
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002868:Chromosomal Proteins, Non-Histone; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006655:Histone Deacetylases / Q000378:metabolism*; D051783:Methyl-CpG-Binding Protein 2; D008969:Molecular Sequence Data; D012097:Repressor Proteins / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D029867:Xenopus Proteins; D014982:Xenopus laevis
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C497395:MECP2 protein, Xenopus; D051783:Methyl-CpG-Binding Protein 2; D012097:Repressor Proteins; C071731:SIN3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; D006655:Histone Deacetylases