KDM3B Is the H3K9 Demethylase Involved in Transcriptional Activation of lmo2 in Leukemia

被引：102

作者：

Kim, Ji-Young ^{[1
]}

Kim, Kee-Beom ^{[1
]}

Eom, Gwang Hyeon ^{[2
,3
]}

Choe, Nakwon ^{[2
,3
]}

Kee, Hae Jin ^{[2
,3
]}

Son, Hye-Ju ^{[1
]}

Oh, Si-Taek ^{[1
]}

Kim, Dong-Wook ^{[4
,5
]}

Pak, Jhang Ho ^{[6
]}

Baek, Hee Jo ^{[7
]}

Kook, Hoon ^{[7
]}

Hahn, Yoonsoo ^{[1
]}

Kook, Hyun ^{[2
,3
]}

Chakravarti, Debabrata ^{[8
,9
]}

Seo, Sang-Beom ^{[1
]}

机构：

[1] Chung Ang Univ, Dept Life Sci, Coll Nat Sci, Seoul 156756, South Korea

[2] Chonnam Natl Univ, Med Res Ctr Gene Regulat, Kwangju, South Korea

[3] Chonnam Natl Univ, Dept Pharmacol, Kwangju, South Korea

[4] Chonbuk Natl Univ, Dept Oral Pharmacol, Sch Dent, Jeonju, South Korea

[5] Chonbuk Natl Univ, Inst Oral Biosci, Jeonju, South Korea

[6] Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea

[7] Chonnam Natl Univ, Hwasun Hosp, Dept Pediat, Hwasun, South Korea

[8] Northwestern Univ, Feinberg Sch Med, Div Reprod Biol Res, Dept Obstet & Gynecol, Chicago, IL 60611 USA

[9] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA

来源：

MOLECULAR AND CELLULAR BIOLOGY | 2012年 / 32卷 / 14期

基金：

新加坡国家研究基金会;

关键词：

HISTONE H3; GENE-EXPRESSION; PROMYELOCYTIC LEUKEMIA; BINDING-PROTEIN; DIFFERENTIATION; CANCER; PROLIFERATION; METHYLATION; CHROMATIN; JHDM2A;

D O I：

10.1128/MCB.00133-12

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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 Imo2 through interdependent actions with the histone acetyltransferase (HAT) complex containing CBP.

引用

页码：2917 / 2933

页数：17

共 32 条

[1]

SetDB1 contributes to repression of genes encoding developmental regulators and maintenance of ES cell state [J].