Jmjd2c histone demethylase enhances the expression of Mdm2 oncogene.
Jmjd2c is a candidate oncogene that encodes histone lysine demethylase. In this study, we discovered that over-expression of Jmjd2c increased the expression of Mdm2 oncogene dependent on its demethylase activity, which led to the reduction of p53 tumor suppressor gene product in the cells. A chromatin immunoprecipitation assay showed that Jmjd2c was recruited to the P2 promoter region of Mdm2 gene resulting in demethylation of histone H3 lysine 9, as typically found in actively transcribed genes. Furthermore, siRNA-mediated knockdown of Jmjd2c caused the reduction of Mdm2 expression in the cells. These results indicate that Mdm2 oncogene is a downstream target of Jmjd2c and may play an important role in Jmjd2c-mediated oncogenesis.
Ishimura
Akihiko
A
Division of Functional Genomics, Molecular & Cellular Targeting Translational Oncology Center, Cancer Research Institute, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan.
Terashima
Minoru
M
Kimura
Hiroshi
H
Akagi
Keiko
K
Suzuki
Yutaka
Y
Sugano
Sumio
S
Suzuki
Takeshi
T
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D056484:Jumonji Domain-Containing Histone Demethylases; D008745:Methylation; D051379:Mice; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*
D006657:Histones; C544194:Jmjd2c protein, mouse; D056484:Jumonji Domain-Containing Histone Demethylases; D010089:Oxidoreductases, N-Demethylating; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2; D006655:Histone Deacetylases