The Histone Demethylase JMJD2C Is Stage-Specifically Expressed in Preimplantation Mouse Embryos and Is Required for Embryonic Development

被引:65
作者
Wang, Jianle [1 ,2 ,3 ]
Zhang, Miao [1 ]
Zhang, Yu [1 ]
Kou, Zhaohui [1 ]
Han, Zhiming [2 ]
Chen, Da-Yuan [2 ]
Sun, Qing-Yuan [2 ]
Gao, Shaorong [1 ]
机构
[1] Natl Inst Biol Sci, Beijing 102206, Peoples R China
[2] Chinese Acad Sci, Inst Zool, State Key Lab Reprod Biol, Beijing, Peoples R China
[3] Chinese Acad Sci, Grad Sch, Beijing, Peoples R China
关键词
developmental biology; early development; embryo; embryonic development; histone demethylase; JMJD2C; RNAi; DOMAIN-CONTAINING PROTEINS; C-MYC; GENE-EXPRESSION; PATERNAL GENOME; ES CELLS; FAMILY; TRANSCRIPTION; METHYLATION; LYSINE-9; JHDM2A;
D O I
10.1095/biolreprod.109.078055
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Epigenetic modifications play a pivotal role in embryonic development by dynamically regulating DNA methylation and chromatin modifications. Although recent studies have shown that core histone methylation is reversible, very few studies have investigated the functions of the newly discovered histone demethylases during embryonic development. In the present study, we investigated the expression characteristics and function of JMJD2C, a histone demethylase that belongs to the JmjC-domain-containing histone demethylases, during preimplantation embryonic development of the mouse. We found that JMJD2C is stage-specifically expressed during preimplantation development, with the highest activity being observed from the two-cell to the eight-cell stage. Depletion of JMJD2C in metaphase II oocytes followed by parthenogenetic activation causes a developmental arrest before the blastocyst stage. Moreover, consistent with a previous finding in embryonic stem (ES) cells, depletion of JMJD2C causes a significant down-regulation of the pluripotency gene Nanog in embryos. However, contrary to a previous report in ES cells, we observed that other pluripotency genes, Pou5f1 and Sox2, are also significantly down-regulated in JMJD2C-depleted embryos. Furthermore, the depletion of JMJD2C in early embryos also caused significant down- regulation of the Myc and Klf4 genes, which are associated with cell proliferation. Our data suggest that the deregulation of these critical genes synergistically causes the developmental defects observed in JMJD2C-depleted embryos.
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页码:105 / 111
页数:7
相关论文
共 38 条
[1]   Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3-9 encode centromere-associated proteins which complex with the heterochromatin component M31 [J].
Aagaard, L ;
Laible, G ;
Selenko, P ;
Schmid, M ;
Dorn, R ;
Schotta, G ;
Kuhfittig, S ;
Wolf, A ;
Lebersorger, A ;
Singh, PB ;
Reuter, G ;
Jenuwein, T .
EMBO JOURNAL, 1999, 18 (07) :1923-1938
[2]   UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development [J].
Agger, Karl ;
Cloos, Paul A. C. ;
Christensen, Jesper ;
Pasini, Diego ;
Rose, Simon ;
Rappsilber, Juri ;
Issaeva, Irina ;
Canaani, Eli ;
Salcini, Anna Elisabetta ;
Helin, Kristian .
NATURE, 2007, 449 (7163) :731-U10
[3]   c-Myc is essential for vasculogenesis and angiogenesis during development and tumor progression [J].
Baudino, TA ;
McKay, C ;
Pendeville-Samain, H ;
Nilsson, JA ;
Maclean, KH ;
White, EL ;
Davis, AC ;
Ihle, JN ;
Cleveland, JL .
GENES & DEVELOPMENT, 2002, 16 (19) :2530-2543
[4]   RBP2 belongs to a family of demethylases, specific for tri- and dimethylated lysine 4 on histone 3 [J].
Christensen, Jesper ;
Agger, Karl ;
Cloos, Paul A. C. ;
Pasini, Diego ;
Rose, Simon ;
Sennels, Lau ;
Rappsilber, Juri ;
Hansen, Klaus H. ;
Salcini, Anna Elisabetta ;
Helin, Kristian .
CELL, 2007, 128 (06) :1063-1076
[5]   The putative oncogene GASC1 demethylates tri- and dimethylated lysine 9 on histone H3 [J].
Cloos, Paul A. C. ;
Christensen, Jesper ;
Agger, Karl ;
Maiolica, Alessio ;
Rappsilber, Juri ;
Antal, Torben ;
Hansen, Klaus H. ;
Helin, Kristian .
NATURE, 2006, 442 (7100) :307-311
[6]   HUMAN C-MYC ONC GENE IS LOCATED ON THE REGION OF CHROMOSOME-8 THAT IS TRANSLOCATED IN BURKITT-LYMPHOMA CELLS [J].
DALLAFAVERA, R ;
BREGNI, M ;
ERIKSON, J ;
PATTERSON, D ;
GALLO, RC ;
CROCE, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1982, 79 (24) :7824-7827
[7]   Analysis of C-MYC function in normal cells via conditional gene-targeted mutation [J].
de Alboran, IM ;
O'Hagan, RC ;
Gärtner, F ;
Malynn, B ;
Davidson, L ;
Rickert, R ;
Rajewsky, K ;
DePinho, RA ;
Alt, FW .
IMMUNITY, 2001, 14 (01) :45-55
[8]   Conservation of methylation reprogramming in mammalian development: Aberrant reprogramming in cloned embryos [J].
Dean, W ;
Santos, F ;
Stojkovic, M ;
Zakhartchenko, V ;
Walter, J ;
Wolf, E ;
Reik, W .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (24) :13734-13738
[9]   THE MYC PROTEIN ACTIVATES TRANSCRIPTION OF THE ALPHA-PROTHYMOSIN GENE [J].
EILERS, M ;
SCHIRM, S ;
BISHOP, JM .
EMBO JOURNAL, 1991, 10 (01) :133-141
[10]   The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases [J].
Iwase, Shigeki ;
Lan, Fei ;
Bayliss, Peter ;
de la Torre-Ubieta, Luis ;
Huarte, Maite ;
Qi, Hank H. ;
Whetstine, Johnathan R. ;
Bonni, Azad ;
Roberts, Thomas M. ;
Shi, Yang .
CELL, 2007, 128 (06) :1077-1088