A component of the transcriptional repressor MeCP1 shares a motif with DNA methyltransferase and HRX proteins.
Methylation of cytosines within the sequence CpG is essential for mouse development and has been linked to transcriptional suppression in vertebrate systems. Methyl-CpG binding proteins (MeCPs) 1 and 2 bind preferentially to methylated DNA and can inhibit transcription. The gene for MeCP2 has been cloned and a methyl-CpG binding domain (MBD) within it has been defined. A search of DNA sequence databases with the MBD sequence identified a human cDNA with potential to encode an MBD-like region. Sequencing of the complete cDNA revealed that the open reading frame also encodes two cysteine-rich domains that are found in animal DNA methyltransferases (DNMTs) and in the mammalian HRX protein (also known as MLL and All-1). HRX is related to Drosophila trithorax. The protein, known as Protein Containing MBD (PCM1), was expressed in bacteria and shown to bind specifically to methylated DNA. PCM1 also repressed transcription in vitro in a methylation-dependent manner. A polyclonal antibody raised against the protein was able to 'supershift' the native MeCP11 complex from HeLa cells, indicating that PCM1 is a component of mammalian MeCP1.
Cross
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Institute of Cell and Molecular Biology, Edinburgh University U.K. Sally.Cross@ed.ac.uk and A.Bird@ed.ac.uk
Meehan
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Nan
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Bird
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A
D000595:Amino Acid Sequence; D002868:Chromosomal Proteins, Non-Histone; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000737:chemistry* / Q000378:metabolism; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D015226:Dinucleoside Phosphates / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000235:genetics; D006367:HeLa Cells; D006655:Histone Deacetylases; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein; D009687:Nuclear Proteins / Q000378:metabolism; D011519:Proto-Oncogenes; D011994:Recombinant Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014157:Transcription Factors; D014158:Transcription, Genetic
D002868:Chromosomal Proteins, Non-Histone; D015254:DNA Modification Methylases; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D015226:Dinucleoside Phosphates; D006655:Histone Deacetylases; D011495:Histone-Lysine N-Methyltransferase; D051783:Methyl-CpG-Binding Protein 2; D051788:Myeloid-Lymphoid Leukemia Protein; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C497422:KMT2A protein, human; C497392:MECP2 protein, human; C489689:MeCP1 histone deacetylase complex, human; C489690:MeCP1 histone deacetylase complex, mouse; C015772:CpG dinucleotide