ATP-Citrate Lyase Links Cellular Metabolism to Histone Acetylation

被引：1712

作者：

Wellen, Kathryn E. ^{[1
]}

Hatzivassiliou, Georgia ^{[1
]}

Sachdeva, Uma M. ^{[1
]}

Bui, Thi V. ^{[1
]}

Cross, Justin R. ^{[1
]}

Thompson, Craig B. ^{[1
]}

机构：

[1] Univ Penn, Dept Canc Biol, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA

来源：

SCIENCE | 2009年 / 324卷 / 5930期

关键词：

TRANSCRIPTION; H4; DEACETYLATION; ACETYLTRANSFERASE; SYNTHETASE; ACTIVATION; EXPRESSION; COMPLEXES; DYNAMICS; SIRTUINS;

D O I：

10.1126/science.1164097

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Histone acetylation in single-cell eukaryotes relies on acetyl coenzyme A (acetyl-CoA) synthetase enzymes that use acetate to produce acetyl-CoA. Metazoans, however, use glucose as their main carbon source and have exposure only to low concentrations of extracellular acetate. We have shown that histone acetylation in mammalian cells is dependent on adenosine triphosphate (ATP)-citrate lyase (ACL), the enzyme that converts glucose-derived citrate into acetyl-CoA. We found that ACL is required for increases in histone acetylation in response to growth factor stimulation and during differentiation, and that glucose availability can affect histone acetylation in an ACL-dependent manner. Together, these findings suggest that ACL activity is required to link growth factor-induced increases in nutrient metabolism to the regulation of histone acetylation and gene expression.

引用

页码：1076 / 1080

页数：5

共 31 条

[1] Activation of SRF-regulated chromosomal templates by Rho-family GTPases requires a signal that also induces H4 hyperacetylation [J].

Alberts, AS ;

Geneste, O ;

Treisman, R .

CELL, 1998, 92 (04) :475-487

[2] Post-translational modification of p53 in tumorigenesis [J].

Bode, AM ;

Dong, ZG .

NATURE REVIEWS CANCER, 2004, 4 (10) :793-805

[3] Global histone acetylation induces functional genomic reorganization at mammalian nuclear pore complexes [J].

Brown, Christopher R. ;

Kennedy, Caleb J. ;

Delmar, Valerie A. ;

Forbes, Douglass J. ;

Silver, Pamela A. .

GENES & DEVELOPMENT, 2008, 22 (05) :627-639

[4] Enhanced histone acetylation and transcription: A dynamic perspective [J].

Clayton, Alison L. ;

Hazzalin, Catherine A. ;

Mahadevan, Louis C. .

MOLECULAR CELL, 2006, 23 (03) :289-296

[5] Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase [J].

Cohen, HY ;

Miller, C ;

Bitterman, KJ ;

Wall, NR ;

Hekking, B ;

Kessler, B ;

Howitz, KT ;

Gorospe, M ;

de Cabo, R ;

Sinclair, DA .

SCIENCE, 2004, 305 (5682) :390-392

[6] Histone deacetylases and cancer [J].

Glozak, M. A. ;

Seto, E. .

ONCOGENE, 2007, 26 (37) :5420-5432

[7] Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases [J].

Hallows, William C. ;

Lee, Susan ;

Denu, John M. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (27) :10230-10235

[8] ATP citrate lyase inhibition can suppress tumor cell growth [J].

Hatzivassiliou, G ;

Zhao, FP ;

Bauer, DE ;

Andreadis, C ;

Shaw, AN ;

Dhanak, D ;

Hingorani, SR ;

Tuveson, DA ;

Thompson, CB .

CANCER CELL, 2005, 8 (04) :311-321

[9] Stress-specific role of fission yeast Gcn5 histone acetyltransferase in programming a subset of stress response genes [J].

Johnsson, Anna ;

Xue-Franzen, Yongtao ;

Lundin, Maria ;

Wright, Anthony P. H. .

EUKARYOTIC CELL, 2006, 5 (08) :1337-1346

[10] Myc influences global chromatin structure [J].

Knoepfler, Paul S. ;

Zhang, Xiao-yong ;

Cheng, Pei Feng ;

Gafken, Philip R. ;

McMahon, Steven B. ;

Eisenman, Robert N. .

EMBO JOURNAL, 2006, 25 (12) :2723-2734

← 1 2 3 4 →