KDM3B Is the H3K9 Demethylase Involved in Transcriptional Activation of lmo2 in Leukemia
Author(s) -
Ji-Young Kim,
KeeBeom Kim,
Gwang Hyeon Eom,
Nakwon Choe,
Hae Jin Kee,
Hye-Ju Son,
Si-Taek Oh,
DongWook Kim,
Jhang Ho Pak,
Hee Jo Baek,
Hoon Kook,
Yoonsoo Hahn,
Hyun Kook,
Debabrata Chakravarti,
SangBeom Seo
Publication year - 2012
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.00133-12
Subject(s) - demethylase , biology , chromatin immunoprecipitation , acute promyelocytic leukemia , histone , histone acetyltransferase , corepressor , cancer research , ezh2 , histone methylation , microbiology and biotechnology , myeloid leukemia , retinoic acid , dna methylation , biochemistry , gene expression , repressor , promoter , gene
Histone lysine methylation and demethylation are considered critical steps in transcriptional regulation. In this report, we performed chromatin immunoprecipitation with microarray technology (ChIP-chip) analysis to examine the genome-wide occupancy of H3K9-me2 during all-trans -retinoic acid (ATRA)-induced differentiation of HL-60 promyelocytic leukemia cells. Using this approach, we found that KDM3B, which contains a JmjC domain, was downregulated during differentiation through the recruitment of a corepressor complex. Furthermore, KDM3B displayed histone H3K9-me1/2 demethylase activity and induced leukemogenic oncogenelmo2 expression via a synergistic interaction with CBP. Here, we found that KDM3B repressed leukemia cell differentiation and was upregulated in blood cells from acute lymphoblastic leukemia (ALL)-type leukemia patients. The combined results of this study provide evidence that the H3K9-me1/2 demethylase KDM3B might play a role in leukemogenesis via activation oflmo2 through interdependent actions with the histone acetyltransferase (HAT) complex containing CBP.
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