Identification of Functional Elements and Regulatory Circuits by Drosophila modENCODE

被引：911

作者：

Roy, Sushmita ^{[1
,2
,3
]}

Ernst, Jason ^{[1
,2
,3
]}

Kharchenko, Peter V. ^{[4
]}

Kheradpour, Pouya ^{[1
,2
,3
]}

Negre, Nicolas ^{[5
]}

Eaton, Matthew L. ^{[6
]}

Landolin, Jane M. ^{[7
]}

Bristow, Christopher A. ^{[1
,2
,3
]}

Ma, Lijia ^{[5
]}

Lin, Michael F. ^{[1
,2
,3
]}

Washietl, Stefan ^{[1
]}

Arshinoff, Bradley I. ^{[8
,21
]}

Ay, Ferhat ^{[1
,38
]}

Meyer, Patrick E. ^{[1
,35
]}

Robine, Nicolas ^{[9
]}

Washington, Nicole L. ^{[10
]}

Di Stefano, Luisa ^{[1
,36
]}

Berezikov, Eugene ^{[27
,28
]}

Brown, Christopher D. ^{[5
]}

Candeias, Rogerio ^{[1
]}

Carlson, Joseph W. ^{[7
]}

Carr, Adrian ^{[11
,12
]}

Jungreis, Irwin ^{[1
,2
,3
]}

Marbach, Daniel ^{[1
,2
,3
]}

Sealfon, Rachel ^{[1
,2
,3
]}

Tolstorukov, Michael Y. ^{[4
]}

Will, Sebastian ^{[1
]}

Alekseyenko, Artyom A. ^{[13
,14
]}

Artieri, Carlo ^{[15
]}

Booth, Benjamin W. ^{[7
]}

Brooks, Angela N. ^{[33
]}

Dai, Qi ^{[9
]}

Davis, Carrie A. ^{[16
]}

Duff, Michael O. ^{[17
]}

Feng, Xin ^{[16
,21
,41
]}

Gorchakov, Andrey A. ^{[13
,14
]}

Gu, Tingting ^{[18
]}

Henikoff, Jorja G. ^{[9
]}

Kapranov, Philipp ^{[19
]}

Li, Renhua ^{[20
]}

MacAlpine, Heather K. ^{[6
]}

Malone, John ^{[15
]}

Minoda, Aki ^{[7
]}

Nordman, Jared ^{[26
]}

Okamura, Katsutomo ^{[9
]}

Perry, Marc ^{[21
]}

Powell, Sara K. ^{[6
]}

Riddle, Nicole C. ^{[18
]}

Sakai, Akiko ^{[34
]}

Samsonova, Anastasia ^{[22
,23
]}

机构：

[1] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA

[2] MIT, Broad Inst, Cambridge, MA 02140 USA

[3] Harvard Univ, Cambridge, MA 02140 USA

[4] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA

[5] Univ Chicago, Inst Genom & Syst Biol, Dept Human Genet, Chicago, IL 60637 USA

[6] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA

[7] Lawrence Berkeley Natl Lab, Dept Genome Dynam, Berkeley, CA 94720 USA

[8] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada

[9] Sloan Kettering Inst, New York, NY 10065 USA

[10] LBNL, Genome Sci Div, Berkeley, CA 94720 USA

[11] Univ Cambridge, Dept Genet, Cambridge CB2 3EH, England

[12] Univ Cambridge, Cambridge Syst Biol Ctr, Cambridge CB2 3EH, England

[13] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA

[14] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Genet, Boston, MA 02115 USA

[15] NIDDK, Sect Dev Genom, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA

[16] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA

[17] Univ Connecticut, Stem Cell Inst, Dept Genet & Dev Biol, Farmington, CT 06030 USA

[18] Washington Univ, Dept Biol, St Louis, MO 63130 USA

[19] Affymetrix, Santa Clara, CA 95051 USA

[20] NHGRI, Div Extramural Res, NIH, Bethesda, MD 20892 USA

[21] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada

[22] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[23] Harvard Univ, Sch Med, Drosophila RNAi Screening Ctr, Boston, MA 02115 USA

[24] Washington Univ, Ctr Genome Sci, St Louis, MO 63108 USA

[25] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA

[26] Whitehead Inst, Cambridge, MA 02142 USA

[27] Royal Netherlands Acad Arts & Sci, Hubrecht Inst, Utrecht, Netherlands

[28] Univ Med Ctr Utrecht, Utrecht, Netherlands

[29] Indiana Univ, Ctr Genom & Bioinformat, Bloomington, IN 47405 USA

[30] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA

[31] Univ Calif San Diego, Sect Cell & Dev Biol, Div Biol Sci, La Jolla, CA 92093 USA

[32] Rutgers State Univ, Dept Mol Biol & Biochem, Piscataway, NJ 08854 USA

[33] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA

[34] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

[35] Univ Libre Bruxelles, Machine Learning Grp, B-1050 Brussels, Belgium

[36] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA

[37] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA

[38] Univ Florida, Gainesville, FL 32611 USA

[39] Univ Calif Santa Cruz, Sch Engn, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA

[40] Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA

[41] SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA

来源：

SCIENCE | 2010年 / 330卷 / 6012期

基金：

美国国家科学基金会; 瑞士国家科学基金会; 加拿大自然科学与工程研究理事会; 瑞典研究理事会; 日本学术振兴会;

关键词：

PREDICTIVE CHROMATIN SIGNATURES; TRANSCRIPTION FACTORS; SOMATIC-CELLS; HUMAN GENOME; DNA-BINDING; RNA PATHWAY; MELANOGASTER; SEQUENCE; REGIONS; NETWORK;

D O I：

10.1126/science.1198374

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：

To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage-and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.

引用

页码：1787 / 1797

页数：11

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