Long Noncoding RNA as Modular Scaffold of Histone Modification Complexes

被引：2678

作者：

Tsai, Miao-Chih ^{[1
,2
]}

Manor, Ohad ^{[3
]}

Wan, Yue ^{[1
,2
]}

Mosammaparast, Nima ^{[4
,5
]}

Wang, Jordon K. ^{[1
,2
]}

Lan, Fei ^{[4
,5
,6
]}

Shi, Yang ^{[4
,5
]}

Segal, Eran ^{[3
]}

Chang, Howard Y. ^{[1
,2
]}

机构：

[1] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA

[2] Stanford Univ, Sch Med, Program Epithelial Biol, Stanford, CA 94305 USA

[3] Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel

[4] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA

[5] Childrens Hosp Boston, Dept Med, Div New Born Med, Cambridge, MA 02138 USA

[6] Constellat Pharmaceut, Cambridge, MA 02142 USA

来源：

SCIENCE | 2010年 / 329卷 / 5992期

关键词：

CHROMATIN-STRUCTURE; GENE-EXPRESSION; X-CHROMOSOME; DEMETHYLATION; PROTEIN; CELLS; STATE; LSD1;

D O I：

10.1126/science.1192002

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：

Long intergenic noncoding RNAs (lincRNAs) regulate chromatin states and epigenetic inheritance. Here, we show that the lincRNA HOTAIR serves as a scaffold for at least two distinct histone modification complexes. A 5' domain of HOTAIR binds polycomb repressive complex 2 (PRC2), whereas a 3' domain of HOTAIR binds the LSD1/CoREST/REST complex. The ability to tether two distinct complexes enables RNA-mediated assembly of PRC2 and LSD1 and coordinates targeting of PRC2 and LSD1 to chromatin for coupled histone H3 lysine 27 methylation and lysine 4 demethylation. Our results suggest that lincRNAs may serve as scaffolds by providing binding surfaces to assemble select histone modification enzymes, thereby specifying the pattern of histone modifications on target genes.

引用

页码：689 / 693

页数：5

共 24 条

[1] A bivalent chromatin structure marks key developmental genes in embryonic stem cells [J].

Bernstein, BE ;

Mikkelsen, TS ;

Xie, XH ;

Kamal, M ;

Huebert, DJ ;

Cuff, J ;

Fry, B ;

Meissner, A ;

Wernig, M ;

Plath, K ;

Jaenisch, R ;

Wagschal, A ;

Feil, R ;

Schreiber, SL ;

Lander, ES .

CELL, 2006, 125 (02) :315-326

[2] Mutation of Drosophila Lsd1 disrupts H3-K4 methylation, resulting in tissue-specific defects during development [J].

Di Stefano, Luisa ;

Ji, Jun-Yuan ;

Moon, Nam-Sung ;

Herr, Anabel ;

Dyson, Nicholas .

CURRENT BIOLOGY, 2007, 17 (09) :808-812

[3] Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis [J].

Gupta, Rajnish A. ;

Shah, Nilay ;

Wang, Kevin C. ;

Kim, Jeewon ;

Horlings, Hugo M. ;

Wong, David J. ;

Tsai, Miao-Chih ;

Hung, Tiffany ;

Argani, Pedram ;

Rinn, John L. ;

Wang, Yulei ;

Brzoska, Pius ;

Kong, Benjamin ;

Li, Rui ;

West, Robert B. ;

van de Vijver, Marc J. ;

Sukumar, Saraswati ;

Chang, Howard Y. .

NATURE, 2010, 464 (7291) :1071-U148

[4] Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals [J].

Guttman, Mitchell ;

Amit, Ido ;

Garber, Manuel ;

French, Courtney ;

Lin, Michael F. ;

Feldser, David ;

Huarte, Maite ;

Zuk, Or ;

Carey, Bryce W. ;

Cassady, John P. ;

Cabili, Moran N. ;

Jaenisch, Rudolf ;

Mikkelsen, Tarjei S. ;

Jacks, Tyler ;

Hacohen, Nir ;

Bernstein, Bradley E. ;

Kellis, Manolis ;

Regev, Aviv ;

Rinn, John L. ;

Lander, Eric S. .

NATURE, 2009, 458 (7235) :223-227

[5] Genome-wide mapping of in vivo protein-DNA interactions [J].

Johnson, David S. ;

Mortazavi, Ali ;

Myers, Richard M. ;

Wold, Barbara .

SCIENCE, 2007, 316 (5830) :1497-1502

[6] Polycomb group complexes - many combinations, many functions [J].

Kerppola, Tom K. .

TRENDS IN CELL BIOLOGY, 2009, 19 (12) :692-704

[7] Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression [J].

Khalil, Ahmad M. ;

Guttman, Mitchell ;

Huarte, Maite ;

Garber, Manuel ;

Raj, Arjun ;

Morales, Dianali Rivea ;

Thomas, Kelly ;

Presser, Aviva ;

Bernstein, Bradley E. ;

van Oudenaarden, Alexander ;

Regev, Aviv ;

Lander, Eric S. ;

Rinn, John L. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (28) :11667-11672

[8] Genomewide Analysis of PRC1 and PRC2 Occupancy Identifies Two Classes of Bivalent Domains [J].

Ku, Manching ;

Koche, Richard P. ;

Rheinbay, Esther ;

Mendenhall, Eric M. ;

Endoh, Mitsuhiro ;

Mikkelsen, Tarjei S. ;

Presser, Aviva ;

Nusbaum, Chad ;

Xie, Xiaohui ;

Chi, Andrew S. ;

Adli, Mazhar ;

Kasif, Simon ;

Ptaszek, Leon M. ;

Cowan, Chad A. ;

Lander, Eric S. ;

Koseki, Haruhiko ;

Bernstein, Bradley E. .

PLOS GENETICS, 2008, 4 (10)

[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] Lessons from X-chromosome inactivation: long ncRNA as guides and tethers to the epigenome [J].

Lee, Jeannie T. .

GENES & DEVELOPMENT, 2009, 23 (16) :1831-1842

← 1 2 3 →