Ageing-related chromatin defects through loss of the NURD complex

被引：212

作者：

Pegoraro, Gianluca ^{[1
]}

Kubben, Nard ^{[1
,2
]}

Wickert, Ute ^{[3
]}

Goehler, Heike ^{[4
]}

Hoffmann, Katrin ^{[5
,6
]}

Misteli, Tom ^{[1
]}

机构：

[1] NCI, NIH, Bethesda, MD 20892 USA

[2] Maastricht Univ, Dept Expt & Mol Cardiol, Cardiovasc Res Inst Maastricht, Maastricht, Netherlands

[3] German Canc Res Ctr, Div Mol Genet, D-69120 Heidelberg, Germany

[4] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany

[5] Humboldt Univ, Inst Med Genet, Charite Berlin, D-13353 Berlin, Germany

[6] Max Planck Inst Mol Genet Dev & Dis, D-14195 Berlin, Germany

来源：

NATURE CELL BIOLOGY | 2009年 / 11卷 / 10期

关键词：

PROTEIN-INTERACTION NETWORK; TRANSCRIPTION; ENHANCER; GENOME; BREAKS; CAF-1;

D O I：

10.1038/ncb1971

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Physiological and premature ageing are characterized by multiple defects in chromatin structure and accumulation of persistent DNA damage. Here we identify the NURD chromatin remodelling complex as a key modulator of these ageing-associated chromatin defects. We demonstrate loss of several NURD components during premature and normal ageing and we find an ageing-associated reduction in HDAC1 activity. Silencing of individual NURD subunits recapitulated chromatin defects associated with ageing and we provide evidence that structural chromatin defects precede DNA damage accumulation. These results outline a molecular mechanism for chromatin defects during ageing.

引用

页码：1261 / U251

页数：18

共 26 条

[1] Human laminopathies: nuclei gone genetically awry [J].

Capell, Brian C. ;

Collins, Francis S. .

NATURE REVIEWS GENETICS, 2006, 7 (12) :940-952

[2] Proteomic analysis of the mammalian nuclear pore complex [J].

Cronshaw, JA ;

Krutchinsky, AN ;

Zhang, WZ ;

Chait, BT ;

Matunis, MJ .

JOURNAL OF CELL BIOLOGY, 2002, 158 (05) :915-927

[3] Lamin A truncation in Hutchinson-Gilford progeria [J].

De Sandre-Giovannoli, A ;

Bernard, R ;

Cau, P ;

Navarro, C ;

Amiel, J ;

Boccaccio, I ;

Lyonnet, S ;

Stewart, CL ;

Munnich, A ;

Le Merrer, M ;

Lévy, N .

SCIENCE, 2003, 300 (5628) :2055-2055

[4] Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome [J].

Eriksson, M ;

Brown, WT ;

Gordon, LB ;

Glynn, MW ;

Singer, J ;

Scott, L ;

Erdos, MR ;

Robbins, CM ;

Moses, TY ;

Berglund, P ;

Dutra, A ;

Pak, E ;

Durkin, S ;

Csoka, AB ;

Boehnke, M ;

Glover, TW ;

Collins, FS .

NATURE, 2003, 423 (6937) :293-298

[5] A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's disease [J].

Goehler, H ;

Lalowski, M ;

Stelzl, U ;

Waelter, S ;

Stroedicke, M ;

Worm, U ;

Droege, A ;

Lindenberg, KS ;

Knoblich, M ;

Haenig, C ;

Herbst, M ;

Suopanki, J ;

Scherzinger, E ;

Abraham, C ;

Bauer, B ;

Hasenbank, R ;

Fritzsche, A ;

Ludewig, AH ;

Buessow, K ;

Coleman, SH ;

Gutekunst, CA ;

Landwehrmeyer, BG ;

Lehrach, H ;

Wanker, EE .

MOLECULAR CELL, 2004, 15 (06) :853-865

[6] Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome [J].

Goldman, RD ;

Shumaker, DK ;

Erdos, MR ;

Eriksson, M ;

Goldman, AE ;

Gordon, LB ;

Gruenbaum, Y ;

Khuon, S ;

Mendez, M ;

Varga, R ;

Collins, FS .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (24) :8963-8968

[7] Mis16 and Mis18 are required for CENP-A loading and histone deacetylation at centromeres [J].

Hayashi, T ;

Fujita, Y ;

Iwasaki, O ;

Adachi, Y ;

Takahashi, K ;

Yanagida, M .

CELL, 2004, 118 (06) :715-729

[8] The histone methyltransferase SET8 is required for S-phase progression [J].

Jorgensen, Stine ;

Elvers, Ingegerd ;

Trelle, Morten Beck ;

Menzel, Tobias ;

Eskildsen, Morten ;

Jensen, Ole Norregaard ;

Helleday, Thomas ;

Helin, Kristian ;

Sorensen, Claus Storgaard .

JOURNAL OF CELL BIOLOGY, 2007, 179 (07) :1337-1345

[9] Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein [J].

Kuzmichev, A ;

Nishioka, K ;

Erdjument-Bromage, H ;

Tempst, P ;

Reinberg, D .

GENES & DEVELOPMENT, 2002, 16 (22) :2893-2905

[10] Genomic instability in laminopathy-based premature aging [J].

Liu, BH ;

Wang, JM ;

Chan, KM ;

Tjia, WM ;

Deng, W ;

Guan, XY ;

Huang, JD ;

Li, KM ;

Chau, PY ;

Chen, DJ ;

Pei, DQ ;

Pendas, AM ;

Cadiñanos, J ;

López-Otín, C ;

Tse, HF ;

Hutchison, C ;

Chen, JJ ;

Cao, YH ;

Cheah, KSE ;

Tryggvason, K ;

Zhou, ZJ .

NATURE MEDICINE, 2005, 11 (07) :780-785

← 1 2 3 →