DNMT3B

Description

The DNMT3B (DNA methyltransferase 3 beta) is a protein-coding gene located on chromosome 20.

DNMT3B is an enzyme that in humans is encoded by the DNMT3B gene. Mutation in this gene are associated with immunodeficiency, centromere instability and facial anomalies syndrome. CpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. Studies in mice have demonstrated that DNA methylation is required for mammalian development. This gene encodes a DNA methyltransferase which is thought to function in de novo methylation, rather than maintenance methylation. The protein localizes primarily to the nucleus and its expression is developmentally regulated. Eight alternatively spliced transcript variants have been described. The full length sequences of variants 4 and 5 have not been determined. Immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome is a result of defects in lymphocyte maturation resulting from aberrant DNA methylation caused by mutations in the DNMT3B gene. Variants of the gene can also contribute to nicotine dependency.

DNMT3B is crucial for establishing methylation patterns throughout the genome during development. This process involves creating new methylation marks, known as 'de novo' methylation. DNA methylation is intricately linked with histone methylation, suggesting a coordinated regulatory mechanism. DNMT3B might preferentially modify DNA within the nucleosome core region, which is the fundamental unit of DNA packaging. It can act as a transcriptional repressor by interacting with CBX4, even in the absence of DNA methylation. DNMT3B appears to be involved in silencing gene expression. In collaboration with DNMT1, and through the recruitment of CTCFL/BORIS, DNMT3B participates in activating BAG1 gene expression by altering the methylation status of histone H3 at specific positions (H3K4 and H3K9) within the gene's promoter. Isoforms 4 and 5 of DNMT3B are likely non-functional due to the loss of two important methyltransferase domains. Furthermore, DNMT3B acts as a transcriptional repressor by associating with ZHX1. It is necessary for silencing the DUX4 gene in non-reproductive cells (PubMed:27153398).

DNMT3B is also known as FSHD4, ICF, ICF1, M.HsaIIIB.

Associated Diseases

• Facioscapulohumeral muscular dystrophy 4, digenic
• Immunodeficiency-Centromeric instability-facial anomalies syndrome
• Facioscapulohumeral dystrophy
• ICF syndrome