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 transcription^3–6. 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 trithorax^9,10. 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.