The tumor suppressor Rb and its related Rbl2 genes are regulated by Utx histone demethylase.
Utx is a candidate tumor suppressor gene that encodes histone H3 lysine 27 (H3K27) demethylase. In this study, we found that ectopic expression of Utx enhanced the expression of retinoblastoma tumor suppressor gene Rb and its related gene Rbl2. This activation was dependent on the demethylase activity of Utx, and was suggested to contribute to the decreased cell proliferation induced by Utx. A chromatin immunoprecipitation assay showed that over-expressed Utx was associated with the promoter regions of Rb and Rbl2 resulting in the removal of repressive H3K27 tri-methylation and the increase in active H3K4 tri-methylation. Furthermore, siRNA-mediated knockdown of Utx revealed the recruitment of endogenous Utx protein on the promoters of Rb and Rbl2 genes. These results indicate that Rb and Rbl2 are downstream target genes of Utx and may play important roles in Utx-mediated cell growth control.
Terashima
Minoru
M
Division of Functional Genomics, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Ishikawa, Japan.
Ishimura
Akihiko
A
Yoshida
Masakazu
M
Suzuki
Yutaka
Y
Sugano
Sumio
S
Suzuki
Takeshi
T
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D056466:Histone Demethylases; D006657:Histones / Q000378:metabolism; D008745:Methylation; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D016160:Retinoblastoma Protein / Q000235:genetics*; D050717:Retinoblastoma-Like Protein p130 / Q000235:genetics*
D006657:Histones; D009687:Nuclear Proteins; D016160:Retinoblastoma Protein; D050717:Retinoblastoma-Like Protein p130; D056466:Histone Demethylases; C111778:Utx protein, mouse