DNMT3B

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. Mutations in this gene cause the immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome. Eight alternatively spliced transcript variants have been described. The full length sequences of variants 4 and 5 have not been determined. [provided by RefSeq, May 2011]

Full Name

DNA Methyltransferase 3 Beta

Function

Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. May preferentially methylates nucleosomal DNA within the nucleosome core region. May function as transcriptional co-repressor by associating with CBX4 and independently of DNA methylation. Seems to be involved in gene silencing (By similarity).

In association with DNMT1 and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. Isoforms 4 and 5 are probably not functional due to the deletion of two conserved methyltransferase motifs. Functions as a transcriptional corepressor by associating with ZHX1. Required for DUX4 silencing in somatic cells (PubMed:27153398).

Biological Process

Cellular response to dexamethasone stimulus Source: Ensembl
Cellular response to hyperoxia Source: Ensembl
DNA methylation Source: UniProtKB
Negative regulation of histone H3-K9 methylation Source: UniProtKB
Negative regulation of transcription by RNA polymerase II Source: UniProtKB
Positive regulation of gene expression Source: UniProtKB
Positive regulation of histone H3-K4 methylation Source: UniProtKB
Positive regulation of neuron differentiation Source: Ensembl
Response to activity Source: Ensembl
Response to caffeine Source: Ensembl
Response to cocaine Source: Ensembl
Response to drug Source: Ensembl
Response to estradiol Source: Ensembl
Response to hypoxia Source: Ensembl
Response to ionizing radiation Source: Ensembl
Response to toxic substance Source: Ensembl
Response to vitamin A Source: Ensembl

Cellular Location

Nucleus

Involvement in disease

Immunodeficiency-centromeric instability-facial anomalies syndrome 1 (ICF1):
A rare disorder characterized by a variable immunodeficiency resulting in recurrent infections, facial anomalies, and branching of chromosomes 1, 9, and 16. Other variable symptoms include growth retardation, failure to thrive, and psychomotor retardation. Laboratory studies show limited hypomethylation of DNA in a small fraction of the genome in some, but not all, patients.
Facioscapulohumeral muscular dystrophy 2 (FSHD2):
The gene represented in this entry may act as a disease modifier. DNMT3B mutations lead to DUX4 expression in somatic tissues, including muscle cells, when an haplotype on chromosome 4 is permissive for DUX4 expression. Ectopic expression of DUX4 in skeletal muscle activates the expression of stem cell and germline genes, and, when overexpressed in somatic cells, DUX4 can ultimately lead to cell death. A degenerative muscle disease characterized by slowly progressive weakness of the muscles of the face, upper-arm, and shoulder girdle. The onset of symptoms usually occurs in the first or second decade of life. Affected individuals usually present with impairment of upper extremity elevation. This tends to be followed by facial weakness, primarily involving the orbicularis oris and orbicularis oculi muscles.

PTM

Sumoylated.
Citrullinated by PADI4.