DNMT3L

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 nuclear protein with similarity to DNA methyltransferases, but is not thought to function as a DNA methyltransferase as it does not contain the amino acid residues necessary for methyltransferase activity. However, it does stimulate de novo methylation by DNA cytosine methyltransferase 3 alpha and is thought to be required for the establishment of maternal genomic imprints. This protein also mediates transcriptional repression through interaction with histone deacetylase 1. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2012]

Full Name

DNA Methyltransferase 3 Like

Function

Catalytically inactive regulatory factor of DNA methyltransferases that can either promote or inhibit DNA methylation depending on the context (By similarity).

Essential for the function of DNMT3A and DNMT3B: activates DNMT3A and DNMT3B by binding to their catalytic domain (PubMed:17687327).

Acts by accelerating the binding of DNA and S-adenosyl-L-methionine (AdoMet) to the methyltransferases and dissociates from the complex after DNA binding to the methyltransferases (PubMed:17687327).

Recognizes unmethylated histone H3 lysine 4 (H3K4me0) and induces de novo DNA methylation by recruitment or activation of DNMT3 (PubMed:17687327).

Plays a key role in embryonic stem cells and germ cells (By similarity).

In germ cells, required for the methylation of imprinted loci together with DNMT3A (By similarity).

In male germ cells, specifically required to methylate retrotransposons, preventing their mobilization (By similarity).

Plays a key role in embryonic stem cells (ESCs) by acting both as an positive and negative regulator of DNA methylation (By similarity).

While it promotes DNA methylation of housekeeping genes together with DNMT3A and DNMT3B, it also acts as an inhibitor of DNA methylation at the promoter of bivalent genes (By similarity).

Interacts with the EZH2 component of the PRC2/EED-EZH2 complex, preventing interaction of DNMT3A and DNMT3B with the PRC2/EED-EZH2 complex, leading to maintain low methylation levels at the promoters of bivalent genes (By similarity).

Promotes differentiation of ESCs into primordial germ cells by inhibiting DNA methylation at the promoter of RHOX5, thereby activating its expression (By similarity).

Biological Process

DNA methylation Source: UniProtKB
DNA methylation involved in gamete generation Source: UniProtKB
DNA methylation on cytosine Source: UniProtKB
Male meiosis I Source: UniProtKB
Negative regulation of DNA methylation Source: UniProtKB
Negative regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of DNA methylation Source: UniProtKB
Regulation of gene expression by genetic imprinting Source: UniProtKB
Spermatogenesis Source: UniProtKB
Stem cell differentiation Source: UniProtKB

Cellular Location

Nucleus