GADD45A does not promote DNA demethylation

被引:118
作者
Jin, Seung-Gi [1 ]
Guo, Cai [1 ]
Pfeifer, Gerd P. [1 ]
机构
[1] Beckman Res Inst City Hope, Div Biol, Duarte, CA USA
来源
PLOS GENETICS | 2008年 / 4卷 / 03期
关键词
D O I
10.1371/journal.pgen.1000013
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Although DNA methylation patterns in somatic cells are thought to be relatively stable, they undergo dramatic changes during embryonic development, gametogenesis, and during malignant transformation. The enzymology of DNA methyltransferases is well understood, but the mechanism that removes methylated cytosines from DNA (active DNA demethylation) has remained enigmatic. Recently, a role of the growth arrest and DNA damage inducible protein GADD45A in DNA demethylation has been reported [1]. We have investigated the function of GADD45A in DNA demethylation in more detail using gene reactivation and DNA methylation assays. Contrary to the previous report, we were unable to substantiate a functional role of GADD45A in DNA demethylation. The mechanism of active DNA demethylation in mammalian cells remains unknown.
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页数:9
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共 34 条
[1]   Role of the Arabidopsis DNA glycosylase/lyase ROS1 in active DNA demethylation [J].
Agius, Fernanda ;
Kapoor, Avnish ;
Zhu, Jian-Kang .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (31) :11796-11801
[2]   MEDEA takes control of its own imprinting [J].
Arnaud, P ;
Feil, R .
CELL, 2006, 124 (03) :468-470
[3]   Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation [J].
Barreto, Guillermo ;
Schaefer, Andrea ;
Marhold, Joachim ;
Stach, Dirk ;
Swaminathan, Suresh K. ;
Handa, Vikas ;
Doederlein, Gabi ;
Maltry, Nicole ;
Wu, Wei ;
Lyko, Frank ;
Niehrs, Christof .
NATURE, 2007, 445 (7128) :671-675
[4]   A mammalian protein with specific demethylase activity for mCpG DNA [J].
Bhattacharya, SK ;
Ramchandani, S ;
Cervoni, N ;
Szyf, M .
NATURE, 1999, 397 (6720) :579-583
[5]   ESTABLISHMENT OF A HUMAN CELL-LINE FOR THE DETECTION OF DEMETHYLATING AGENTS [J].
BIARD, DSF ;
CORDIER, A ;
SARASIN, A .
EXPERIMENTAL CELL RESEARCH, 1992, 200 (02) :263-271
[6]   Demethylase activity is directed by histone acetylation [J].
Cervoni, N ;
Szyf, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (44) :40778-40787
[7]   DEMETER DNA glycosylase establishes MEDEA polycomb gene self-imprinting by allele-specific demethylation [J].
Gehring, M ;
Huh, JH ;
Hsieh, TF ;
Penterman, J ;
Choi, Y ;
Harada, JJ ;
Goldberg, RB ;
Fischer, RL .
CELL, 2006, 124 (03) :495-506
[8]   A unique developmental pattern of Oct-3/4 DNA methylation is controlled by a cis-demodification element [J].
Gidekel, S ;
Bergman, Y .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (37) :34521-34530
[9]   Genomic instability, centrosome amplification, cell cycle checkpoints and Gadd45a [J].
Hollander, MC ;
Fornace, AJ .
ONCOGENE, 2002, 21 (40) :6228-6233
[10]   MBD3L1 and MBD3L2, two new proteins homologous to the methyl-CpG-binding proteins MBD2 and MBD3:: Characterization of MBD3L1 as a testis-specific transcriptional repressor [J].
Jiang, CL ;
Jin, SG ;
Lee, DH ;
Lan, ZJ ;
Xu, XP ;
O'Connor, TR ;
Szabó, PE ;
Mann, JR ;
Cooney, AJ ;
Pfeifer, GP .
GENOMICS, 2002, 80 (06) :621-629