DNA methyltransferase 3B acts as a co-repressor of the human polycomb protein hPc2 to repress fibroblast growth factor receptor 3 transcription.
DNA methyltransferase 3B has been demonstrated to mediate gene silencing. The mechanisms how DNA methyltransferase 3B is targeted to specific regions and represses gene transcription, however, are not well understood. Here we show that by using yeast two-hybrid screening, DNA methyltransferase 3B interacts with the human polycomb protein, hPc2. This interaction was verified via co-immunoprecipitation and GST pull-down assay. Sequential deletion analysis showed that the region of DNA methyltransferase 3B responsible for interaction is mapped to the N-terminal regulatory domain. By performing a cDNA microarray analysis in HCT 116 cells, we identified that the expression of fibroblast growth factor receptor 3 is significantly increased upon the small interference RNA-mediated knockdown of hPc2, suggesting fibroblast growth factor receptor 3 as a potential target of hPc2. We further found that DNA methyltransferase 3B enhances hPc2-mediated transcriptional repression of fibroblast growth factor receptor 3, which does not require its de novo methyltransferase activity. Taken together, these results suggest that DNA methyltransferase 3B functions as a co-repressor of polycomb protein in inducing transcriptional repression independent of DNA methylation.
Kim
Sung-Hak
SH
National Research Laboratory for Cancer Epigenetics, Cancer Research Institute, Republic of Korea.
Park
Jinah
J
Choi
Moon-Chang
MC
Park
Jung-Hyun
JH
Kim
Hwang-Phill
HP
Lee
Ju-Hee
JH
Oh
Do-Youn
DY
Im
Seock-Ah
SA
Bang
Yung-Jue
YJ
Kim
Tae-You
TY
D000818:Animals; D002460:Cell Line; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D008025:Ligases; D063146:Polycomb-Group Proteins; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases; D000097584:DNA Methyltransferase 3B
D004248:DNA (Cytosine-5-)-Methyltransferases; D008025:Ligases; D063146:Polycomb-Group Proteins; D034741:RNA, Small Interfering; D051498:Receptor, Fibroblast Growth Factor, Type 3; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D044767:Ubiquitin-Protein Ligases; D000097584:DNA Methyltransferase 3B; C496365:FGFR3 protein, human; C570427:CBX4 protein, human