KDM8, a H3K36me2 histone demethylase that acts in the cyclin A1 coding region to regulate cancer cell proliferation

Datsun A. Hsia, Clifford G. Tepper, Mamata R. Pochampalli, Elaine Y.C. Hsia, Chie Izumiya, Steve B. Huerta, Michael E. Wright, Hong Wu Chen, Hsing Jien Kung, Yoshihiro Izumiya

研究成果: 雜誌貢獻文章同行評審

137 引文 斯高帕斯(Scopus)

摘要

Localized chromatin modifications of histone tails play an important role in regulating gene transcription, and aberration of these processes leads to carcinogenesis. Methylated histone lysine residues, a key player in chromatin remodeling, are demethylated by the JmjC class of enzymes. Here weshow that JMJD5 (now renamed KDM8), a JmjC family member, demethylates H3K36me2 and is required for cell cycle progression. Chromatin immunoprecipitation assays applied to human genome tiling arrays in conjunction with RNA microarray revealed that KDM8 occupies the coding region of cyclin A1 and directly regulates transcription. Mechanistic analyses showed that KDM8 functioned as a transcriptional activator by inhibiting HDAC recruitment via demethylation of H3K36me2, an epigenetic repressive mark. Tumor array experiments revealed KDM8 is overexpressed in several types of cancer. In addition, loss-of-function studies in MCF7 cells leads to cell cycle arrest. These studies identified KDM8 as an important cell cycle regulator.
原文英語
頁(從 - 到)9671-9676
頁數6
期刊Proceedings of the National Academy of Sciences of the United States of America
107
發行號21
DOIs
出版狀態已發佈 - 5月 25 2010
對外發佈

ASJC Scopus subject areas

  • 多學科

指紋

深入研究「KDM8, a H3K36me2 histone demethylase that acts in the cyclin A1 coding region to regulate cancer cell proliferation」主題。共同形成了獨特的指紋。

引用此