The tumor suppressor Rb and its related Rbl2 genes are regulated by Utx histone demethylase.
The tumor suppressor Rb and its related Rbl2 genes are regulated by Utx histone demethylase.
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DOI：
10.1016/j.bbrc.2010.07.061
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发表时间：
2010-08
影响因子：
3.1
通讯作者：
Minoru Terashima;A. Ishimura;Masakazu Yoshida;Yutaka Suzuki;S. Sugano;Takeshisa Suzuki
中科院分区：
文献类型：
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作者：
Minoru Terashima;A. Ishimura;Masakazu Yoshida;Yutaka Suzuki;S. Sugano;Takeshisa Suzuki
UTX是编码组蛋白H3赖氨酸27(H3K27)去甲基酶的候选抑癌基因。在本研究中，我们发现UTX的异位表达增强了视网膜母细胞瘤抑癌基因Rb及其相关基因Rbl2的表达。这种激活依赖于UTX的脱甲基酶活性，这可能是UTX诱导的细胞增殖下降的原因之一。染色质免疫沉淀分析表明，过表达的UTX与Rb和Rbl2的启动子区域相关，导致抑制的H3K27三甲基化被去除，而活性的H3K4三甲基化增加。此外，siRNA介导的UTX基因敲除揭示了内源性UTX蛋白在Rb和Rbl2基因启动子上的募集。这些结果表明，Rb和Rbl2是UTX的下游靶基因，可能在UTX介导的细胞生长控制中发挥重要作用。
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.