MBD1

Description

The MBD1 (methyl-CpG binding domain protein 1) is a protein-coding gene located on chromosome 18.

MBD1 is a protein that binds to methylated DNA sequences, influencing gene transcription. It binds to various methylated sequences and appears to repress gene expression. MBD1 contributes to chromatin modification by interacting with the histone H3K9 methyltransferase SETDB1, which is associated with repressive modifications. DNA methylation, a key modification in eukaryotic genomes, is crucial for mammalian development. The MBD family, including MECP2, MBD1, MBD2, MBD3, and MBD4, contains proteins with a methyl-CpG binding domain (MBD). While MBD3 doesn't bind methylated DNA, the other members, including MBD1, can specifically bind to methylated DNA. MECP2, MBD1, and MBD2 can suppress transcription from methylated gene promoters. MBD1 has five transcript variants created through alternative splicing, resulting in protein isoforms with one MBD domain, two to three cysteine-rich (CXXC) domains, and variations in the COOH terminus. All five variants repress transcription from methylated promoters; however, variants with three CXXC domains also suppress activity from unmethylated promoters.

MBD1 acts as a transcriptional repressor by binding to CpG islands within promoters where DNA is methylated at the 5th position of cytosine in CpG dinucleotides. This binding is disrupted by the presence of 7-mG, a modification caused by DNA damage from methylmethanesulfonate (MMS). MBD1 plays a role in gene silencing by recruiting ATF7IP, which in turn recruits factors like the histone methyltransferase SETDB1. It likely forms a complex with SETDB1 and ATF7IP to repress transcription and link DNA methylation with histone 'Lys-9' trimethylation. Notably, isoforms 1 and 2 of MBD1 can also repress transcription from unmethylated promoters.

MBD1 is also known as CXXC3, PCM1, RFT.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing