DNMT3A:DNMT3L methylates cytosine in DNA

Stable Identifier
Homo sapiens
Locations in the PathwayBrowser

DNMT3A methylates the 5 position of cytosine in DNA. As inferred from the mouse homolog, DNMT3A generates asymmetric methylation (methylation of only one strand) of CG dinucleotides and non-CG cytosine residues. DNMT3L interacts with and stimulates the catalytic activity of DNMT3A2 and DNMT3A (Chen et al. 2005, Kareta et al. 2006, Ooi et al. 2007, Holz-Schietinger and Reich 2010). DNMT3A preferentially methylates DNA in regions of transcriptionally active chromatin: DNMT3A-isoform1 transfected into human cells (293T cells) tended to methylate active regions of the genome that were associated with trimethylated lysine-4 of histone H3 (H4K4me3) (Choi et al. 2011). Likewise, in mouse oocytes and embryos CG islands methylated by DNMT3A tend to be located in active transcription units, but with low levels of methylated H3K4 (Smallwood et al. 2011). DNMT3A and its homologue DNMT3B have different preferences for flanking sequences of CG dinucleotides, with DNMT3A tending to methylate sites that have T at the -2 position and C at the +2 position (Wienholz et al. 2010). DNMT3L increases methylation by DNMT3A at sites that are weakly methylated by DNMT3A alone (Wienholz et al. 2010).

Literature References
PubMed ID Title Journal Year
15861382 Physical and functional interactions between the human DNMT3L protein and members of the de novo methyltransferase family

Chen, ZX, Mann, JR, Hsieh, CL, Riggs, AD, Chédin, F

J. Cell. Biochem. 2005
20630873 The inherent processivity of the human de novo methyltransferase 3A (DNMT3A) is enhanced by DNMT3L

Holz-Schietinger, C, Reich, NO

J. Biol. Chem. 2010
21706000 Dynamic CpG island methylation landscape in oocytes and preimplantation embryos

Smallwood, SA, Tomizawa, S, Krueger, F, Ruf, N, Carli, N, Segonds-Pichon, A, Sato, S, Hata, K, Andrews, SR, Kelsey, G

Nat. Genet. 2011
20838592 DNMT3L modulates significant and distinct flanking sequence preference for DNA methylation by DNMT3A and DNMT3B in vivo

Wienholz, BL, Kareta, MS, Moarefi, AH, Gordon, CA, Ginno, PA, Chédin, F

PLoS Genet. 2010
20841325 Identification of preferential target sites for human DNA methyltransferases

Choi, SH, Heo, K, Byun, HM, An, W, Lu, W, Yang, AS

Nucleic Acids Res. 2011
16829525 Reconstitution and mechanism of the stimulation of de novo methylation by human DNMT3L

Kareta, MS, Botello, ZM, Ennis, JJ, Chou, C, Chédin, F

J. Biol. Chem. 2006
Participant Of
Catalyst Activity
Catalyst Activity
DNA (cytosine-5-)-methyltransferase activity, acting on CpN substrates of DNMT3A:DNMT3L:Chromatin [nucleoplasm]
Physical Entity
Inferred From