DNMT3L


Description

The DNMT3L (DNA methyltransferase 3 like) is a protein-coding gene located on chromosome 21.

DNA (cytosine-5)-methyltransferase 3-like is an enzyme that in humans is encoded by the DNMT3L gene.

== Function == 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. This protein is not thought to function as a DNA methyltransferase as it does not contain the amino acid residues necessary for methyltransferase activity. However, this protein does stimulate de novo methylation by DNA cytosine methyltransferase 3 alpha and it is thought to be required for the establishment of maternal genomic imprints. This protein also mediates transcriptional repression through interaction with histone deacetylase 1. Alternative splicing results in two transcript variants. An additional splice variant has been described but its biological validity has not been determined.

== Interactions == DNMT3L has been shown to interact with HDAC1.

DNMT3L is a catalytically inactive regulatory factor of DNA methyltransferases, meaning it doesn't directly add methyl groups to DNA. It plays a complex role in DNA methylation, both promoting and inhibiting it depending on the situation. DNMT3L is crucial for the function of DNMT3A and DNMT3B, activating them by binding to their catalytic domains. It enhances the binding of DNA and S-adenosyl-L-methionine (AdoMet) to these methyltransferases, then detaches after the DNA has bound. DNMT3L can recognize unmethylated histone H3 lysine 4 (H3K4me0), triggering new DNA methylation by recruiting or activating DNMT3. DNMT3L is essential for both embryonic stem cells and germ cells. In germ cells, it's needed for the methylation of imprinted loci alongside DNMT3A. In male germ cells, DNMT3L is particularly important for methylating retrotransposons, preventing their movement. In embryonic stem cells (ESCs), DNMT3L acts as both a positive and negative regulator of DNA methylation. It promotes methylation of housekeeping genes with DNMT3A and DNMT3B, but it also inhibits methylation at the promoters of bivalent genes. DNMT3L interacts with the EZH2 component of the PRC2/EED-EZH2 complex, hindering the interaction of DNMT3A and DNMT3B with this complex, resulting in low methylation levels at the promoters of bivalent genes. DNMT3L promotes the differentiation of ESCs into primordial germ cells by inhibiting methylation at the promoter of RHOX5, thus activating its expression. DNMT3L forms homodimers and also participates in heterotetramers composed of one DNMT3A homodimer and two DNMT3L subunits. It interacts with histone H3 through its N-terminus, but this interaction is strongly inhibited by methylation at lysine 4 (H3K4me). DNMT3L directly interacts with EZH2 and also interacts with SPOCD1.

DNMT3L is also known as -.

Associated Diseases


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