Lung cancer-associated JmjC domain protein mdig suppresses formation of tri-methyl lysine 9 of histone H3.
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.
Lu
Yongju
Y
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA.
Chang
Qingshan
Q
Zhang
Yadong
Y
Beezhold
Kevin
K
Rojanasakul
Yon
Y
Zhao
Hongwen
H
Castranova
Vince
V
Shi
Xianglin
X
Chen
Fei
F
D000595:Amino Acid Sequence; D047369:Chromatin Immunoprecipitation; D049308:Dioxygenases; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D056466:Histone Demethylases; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D054730:Protein Interaction Domains and Motifs; D012318:RNA Polymerase I / Q000378:metabolism; D012335:RNA, Ribosomal / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016415:Sequence Alignment
D044783:F-Box Proteins; D006657:Histones; D009687:Nuclear Proteins; D012335:RNA, Ribosomal; D034741:RNA, Small Interfering; D049308:Dioxygenases; D056466:Histone Demethylases; D056484:Jumonji Domain-Containing Histone Demethylases; C466777:RIOX2 protein, human; C534524:KDM2A protein, human; D010089:Oxidoreductases, N-Demethylating; D012318:RNA Polymerase I; D008239:Lysine