DNA methyltransferase 3-like protein (DNMT3L)

DNA methyltransferase 3-like protein (DNMT3L) is a regulatory protein that lacks intrinsic DNA methyltransferase activity but is essential for the establishment of DNA methylation patterns in mammalian germ cells[1][3][5][6]. DNMT3L interacts directly with Dnmt3a, stimulating its de novo DNA methylation activity, and coordinates with unmethylated histone H3 tails to target chromatin regions for methylation[3][6]. Unlike DNMT3A and DNMT3B, DNMT3L does not possess a catalytic domain and cannot methylate DNA on its own; instead, it serves as a crucial cofactor that enables Dnmt3a to create stable and specific methylation marks at imprinting control regions and other loci critical for proper epigenetic inheritance[1][3][6]. Loss or dysregulation of DNMT3L impairs germ cell development, disrupts genomic imprints, and is associated with disease phenotypes such as infertility and improper gene silencing[1][5]. DNMT3L is therefore viewed as an essential epigenetic regulator, particularly in the establishment and maintenance of genomic imprinting during mammalian reproduction.

Other names

DNA (cytosine-5)-methyltransferase 3-likeDNMT3LMGC1090cytosine-5-methyltransferase 3-like proteinhuman cytosine-5-methyltransferase 3-like protein

Allosteric activation of de novo DNA methyltransferase Dnmt3a (DNMT3L enhances Dnmt3a activity at chromatin)