Histone demethylase JARID1B promotes cell proliferation but is downregulated by N-Myc oncoprotein.
Myc oncoproteins induce tumor initiation and promote tumor progression by modulating gene transcription. We have previously shown that N-Myc represses gene transcription by recruiting histone deacetylases to Sp1-binding site-enriched regions of target gene promoters. The histone demethylase JARID1B plays a dual role in cancer. In the present study, we examined published microarray gene expression datasets and found that JARID1B was commonly repressed by Myc oncoproteins and histone deacetylases in cancer cell lines of various organ origins. Chromatin immunoprecipitation assays demonstrated that N-Myc repressed JARID1B expression by direct binding to the Sp1-binding site-enriched region of the JARID1B gene promoter, and cell proliferation assays showed that transcriptional repression of JARID1B reduced neuroblastoma cell proliferation. Our findings suggest that Myc-mediated transcriptional repression of JARID1B counterintuitively inhibits Myc-regulated cell proliferation and potentially tumorigenesis.
Children's Cancer Institute Australia for Medical Research, Sydney, NSW 2031, Australia.
Lihong
L
Zhang
Children's Cancer Institute Australia for Medical Research, Sydney, NSW 2031, Australia.
Nicolas
N
Sokolowski
Children's Cancer Institute Australia for Medical Research, Sydney, NSW 2031, Australia.
Bernard
B
Atmadibrata
Children's Cancer Institute Australia for Medical Research, Sydney, NSW 2031, Australia.
Tao
T
Liu
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D056484:Jumonji Domain-Containing Histone Demethylases; C119611:KDM5B protein, human