Methyl-CpG-binding protein, MeCP2, is a target molecule for maintenance DNA methyltransferase, Dnmt1.
During mammalian cell division, DNA methylation patterns are transferred accurately to the newly synthesized DNA strand. This depends on maintenance DNA methyltransferase activity. DNA methylation can affect chromatin organization and gene expression by recruitment of histone deacetylases (HDACs). Here we show that the methyl-CpG binding protein, MeCP2, interacts directly with the maintenance DNA methyltransferase, Dnmt1. The region of MeCP2 that interacts with Dnmt1 corresponds to the transcription repressor domain which can also recruit HDACs via a corepressor, mSin3A. Dnmt1 can form complexes with HDACs as well as MeCP2. Surprisingly, the MeCP2-Dnmt1 complex does not contain the histone deacetylase, HDAC1. Thus, Dnmt1 takes the place of the mSin3A-HDAC1 complex, indicating that the MeCP2-interacting Dnmt1 does not bind to HDAC1. Further, we demonstrate that MeCP2 can form a complex with hemimethylated as well as fully methylated DNA. Immunoprecipitated MeCP2 complexes show DNA methyltransferase activity to hemimethylated DNA. These results suggest that Dnmt1 associates with MeCP2 in order to perform maintenance methylation in vivo. We propose that genome-wide and/or -specific local DNA methylation may be maintained by the Dnmt1-MeCP2 complexes, bound to hemimethylated DNA. Dnmt1 may be recruited to targeted regions via multiple steps that may or may not involve histone deacetylases.
Kimura
Hiromichi
H
Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences/Veterinary Medical Sciences, University of Tokyo, Tokyo 113-8657, Japan.
Shiota
Kunio
K
D000818:Animals; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2; D051381:Rats; D012097:Repressor Proteins; D013379:Substrate Specificity
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C497392:MECP2 protein, human; C497394:Mecp2 protein, rat; D051783:Methyl-CpG-Binding Protein 2; D012097:Repressor Proteins; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C000619382:Dnmt1 protein, rat