Lung cancer-associated JmjC domain protein mdig suppresses formation of tri-methyl lysine 9 of histone H3

Yongju Lu, Qingshan Chang, Yadong Zhang, Kevin Beezhold, Yon Rojanasakul, Hongwen Zhao, Vince Castranova, Xianglin Shi, Fei Chen

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

Lung cancer is the most common cancer worldwide, accounting for 1.3 million cancer deaths annually. Despite extensive studies over the past decade, the detailed mechanism about the initiation and development of the lung cancer is still elusive. In the present report, we showed that overexpression of mdig is a common feature of the non-small cell lung cancer. Gene silencing or overexpression of mdig revealed that mdig is involved in demethylation of tri-methyl lysine 9 on histone H3, leading to an increase in ribosomal RNA expression. The transcriptional regulation of ribosomal RNA gene by mdig is achieved through abrogating tri-methyl lysine 9 on histone H3 and enhancing RNA polymerase I occupancy in the promoter region of the ribosomal RNA gene as demonstrated by chromatin immunoprecipitation. The pronounced expression of mdig in lung cancer tissues but not normal lung tissues, thus, suggests that mdig possesses oncogenic property through antagonizing tri-methyl lysine 9 on histone H3 and promoting ribosomal RNA synthesis.

Original languageEnglish
Pages (from-to)2101-2109
Number of pages9
JournalCell Cycle
Volume8
Issue number13
DOIs
StatePublished - Jul 1 2009

Bibliographical note

Funding Information:
We are grateful to Drs. Makoto Tsuneoka (Division of Human Genetics, Department of Forensic Medicine, Kurume University School of Medicine, Fukuoka, Japan) and Marion Schmidt-Zachmann (German Cancer Research Center, Division for Cell Biology, Heidelberg, Germany) for their anti-mdig (mina53, NO52) antibody. This work was supported by an intramural research funding of the National Institute for Occupational Safety and Health (9270036) to F.C. H.Z. is supported by a grant from the National Natural Science Foundation of China (NSFC 30770956).

Keywords

  • H3K9me3
  • Histone demethylation
  • Lung cancer
  • Mineral dust
  • mdig gene

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Lung cancer-associated JmjC domain protein mdig suppresses formation of tri-methyl lysine 9 of histone H3'. Together they form a unique fingerprint.

Cite this