H3K9 histone methyltransferase G9a-mediated transcriptional activation of p21.
We report that H3K9 HMTase G9a activates transcription of the cell cycle regulatory gene, p21, in p53-null H1299 cells. Positive regulation of p21 by G9a is independent of its HMTase activity. We demonstrate that G9a upregulates p21 via interaction with PCAF, and provide evidence that the activating complex is recruited to the p21 promoter upon DNA damage-inducing agent etoposide treatment. Our study suggests that G9a decreases proliferation and cell viability by increasing the level of p21-mediated apoptosis. Our results suggest that G9a functions as a coactivator for p21 transcription, and directs cells to undergo apoptosis.
Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756, South Korea.
Si-Taek
ST
Oh
Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756, South Korea.
Kee-Beom
KB
Kim
Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756, South Korea.
Yun-Cheol
YC
Chae
Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756, South Korea.
Joo-Young
JY
Kang
Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756, South Korea. Electronic address: hahny@cau.ac.kr.
Yoonsoo
Y
Hahn
Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756, South Korea. Electronic address: sangbs@cau.ac.kr.
Sang-Beom
SB
Seo
D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D057809:HEK293 Cells; D006649:Histocompatibility Antigens / Q000502:physiology*; D011495:Histone-Lysine N-Methyltransferase / Q000502:physiology*; D006801:Humans; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D015854:Up-Regulation; D050880:p300-CBP Transcription Factors / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
D050759:Cyclin-Dependent Kinase Inhibitor p21; D006649:Histocompatibility Antigens; D011495:Histone-Lysine N-Methyltransferase; D012333:RNA, Messenger; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C493956:CDKN1A protein, human; C445405:EHMT2 protein, human
Apoptosis; Etoposide; G9a; Transcription; p21