Polycomb protein Cbx4 promotes SUMO modification of de novo DNA methyltransferase Dnmt3a.
The 'de novo methyltransferase' Dnmt3a (DNA methyltransferase 3a) has been shown to mediate transcriptional repression. Post-translational modification of Dnmt3a by SUMOylation affects its ability to transcriptionally repress. However, very little is known about how the SUMOylation process is regulated. In the present study, we identified a PcG (Polycomb group) protein, Cbx4 (chromobox 4), as a specific interaction partner of Dnmt3a. Co-expression of Cbx4 and SUMO-1 (small ubiquitin-related modifier-1) along with Dnmt3a in transfected cells results in enhanced modification of Dnmt3a with SUMO-1. Purified Cbx4 also promotes SUMOylation of Dnmt3a in vitro. The modification occurs in the N-terminal regulatory region, including the PWWP (Pro-Trp-Trp-Pro) domain. Our results suggest that Cbx4 functions as a SUMO E3 ligase for Dnmt3a and it might be involved in the functional regulation of DNA methyltransferases by promoting their SUMO modification.
Li
Bing
B
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, People's Republic of China.
Zhou
Jing
J
Liu
Peng
P
Hu
Jialei
J
Jin
Hong
H
Shimono
Yohei
Y
Takahashi
Masahide
M
Xu
Guoliang
G
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D006570:Heterochromatin / Q000201:enzymology; D006801:Humans; D008025:Ligases; D051379:Mice; D008969:Molecular Sequence Data; D063146:Polycomb-Group Proteins; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000502:physiology*; D025842:SUMO-1 Protein / Q000378:metabolism*; D016415:Sequence Alignment; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
C000717967:DNMT3A protein, human; C000715535:Dnmt3a protein, mouse; D006570:Heterochromatin; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D025842:SUMO-1 Protein; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; C570427:CBX4 protein, human