Identification and functional characterization of the p66/p68 components of the MeCP1 complex.
Methylation of cytosine at CpG dinucleotides is a common feature of many higher eukaryotic genomes. A major biological consequence of DNA methylation is gene silencing. Increasing evidence indicates that recruitment of histone deacetylase complexes by methyl-CpG-binding proteins is a major mechanism of methylated DNA silencing. We have previously reported that the MeCP1 protein complex represses transcription through preferential binding, remodeling, and deacetylation of methylated nucleosomes. To understand the molecular mechanism of the functioning of the MeCP1 complex, the individual components of the MeCP1 complex need to be characterized. In this paper, we report the identification and functional characterization of the p66 and p68 components of the MeCP1 complex. We provide evidence that the two components are different forms of the same zinc finger-containing protein. Analysis of the p66 homologs from different organisms revealed two highly conserved regions, CR1 and CR2. While CR1 is involved in the association of p66 with other MeCP1 components, CR2 plays an important role in targeting p66 and MBD3 to specific loci. Thus, our study not only completes the identification of the MeCP1 components but also reveals the potential function of p66 in MeCP1 complex targeting. The identification and characterization of all the MeCP1 components set the stage for reconstitution of the MeCP1 complex.
Feng
Qin
Q
Department of Biochemistry and Biophysics, Curriculum in Genetics and Molecular Biology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295, USA.
Cao
Ru
R
Xia
Li
L
Erdjument-Bromage
Hediye
H
Tempst
Paul
P
Zhang
Yi
Y
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D017124:Conserved Sequence; D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D020868:Gene Silencing; D006655:Histone Deacetylases; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D016335:Zinc Fingers / Q000235:genetics
D004268:DNA-Binding Proteins; C115369:MBD3 protein, human; D046911:Macromolecular Substances; C492012:Mbd3 protein, rat; C489689:MeCP1 histone deacetylase complex, human; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D006655:Histone Deacetylases