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A component of the transcriptional represser MeCP1 shares a motif with DNA methyltransferase and HRX proteins

Abstract

Methylation of cytosines within the sequence CpG is essential for mouse development1 and has been linked to transcriptional suppression in vertebrate systems2. Methyl-CpG binding proteins (MeCPs) 1 and 2 bind preferentially to methylated DNA and can inhibit transcription3–6. The gene for MeCP2 has been cloned and a methyl-CpG binding domain (MBD) within it has been defined7. 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 MIL and ALL-1)8. HRX is related to Drosophila trithorax9,10. 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 poly-clonal antibody raised against the protein was able to ‘supershift’ the native MeCP1 complex from HeLa cells, indicating that PCM1 is a component of mammalian MeCP1.

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Correspondence to Sally H. Cross.

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Cross, S., Meehan, R., Nan, X. et al. A component of the transcriptional represser MeCP1 shares a motif with DNA methyltransferase and HRX proteins. Nat Genet 16, 256–259 (1997). https://doi.org/10.1038/ng0797-256

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