title: KDM3B is the H3K9 demethylase involved in transcriptional activation of lmo2 in leukemia.
abstract: 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 oncogene lmo2 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 of lmo2 through interdependent actions with the histone acetyltransferase (HAT) complex containing CBP.
authors.affiliation: Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul, Republic of Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Kee-Beom
authors.initials: KB
authors.lastname: Kim
authors.forename: Gwang Hyeon
authors.initials: GH
authors.lastname: Eom
authors.forename: Nakwon
authors.initials: N
authors.lastname: Choe
authors.forename: Hae Jin
authors.initials: HJ
authors.lastname: Kee
authors.forename: Hye-Ju
authors.initials: HJ
authors.lastname: Son
authors.forename: Si-Taek
authors.initials: ST
authors.lastname: Oh
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Jhang Ho
authors.initials: JH
authors.lastname: Pak
authors.forename: Hee Jo
authors.initials: HJ
authors.lastname: Baek
authors.forename: Hoon
authors.initials: H
authors.lastname: Kook
authors.forename: Yoonsoo
authors.initials: Y
authors.lastname: Hahn
authors.forename: Hyun
authors.initials: H
authors.lastname: Kook
authors.forename: Debabrata
authors.initials: D
authors.lastname: Chakravarti
authors.forename: Sang-Beom
authors.initials: SB
authors.lastname: Seo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D057809:HEK293 Cells; D018922:HL-60 Cells; D051548:Histone Acetyltransferases / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D020014:K562 Cells; D060588:LIM Domain Proteins / Q000235:genetics*; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004273:DNA, Neoplasm; D006657:Histones; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D014212:Tretinoin; D056484:Jumonji Domain-Containing Histone Demethylases; C438748:KDM3B protein, human; D051548:Histone Acetyltransferases