Dataset Information

Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project.

ABSTRACT: We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor-binding sites, and maps of chromatin organization. From this, we created more complete and accurate gene models, including alternative splice forms and candidate noncoding RNAs. We constructed hierarchical networks of transcription factor-binding and microRNA interactions and discovered chromosomal locations bound by an unusually large number of transcription factors. Different patterns of chromatin composition and histone modification were revealed between chromosome arms and centers, with similarly prominent differences between autosomes and the X chromosome. Integrating data types, we built statistical models relating chromatin, transcription factor binding, and gene expression. Overall, our analyses ascribed putative functions to most of the conserved genome.

SUBMITTER: Gerstein MB

PROVIDER: S-EPMC3142569 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project.

Gerstein Mark B MB Lu Zhi John ZJ Van Nostrand Eric L EL Cheng Chao C Arshinoff Bradley I BI Liu Tao T Yip Kevin Y KY Robilotto Rebecca R Rechtsteiner Andreas A Ikegami Kohta K Alves Pedro P Chateigner Aurelien A Perry Marc M Morris Mitzi M Auerbach Raymond K RK Feng Xin X Leng Jing J Vielle Anne A Niu Wei W Rhrissorrakrai Kahn K Agarwal Ashish A Alexander Roger P RP Barber Galt G Brdlik Cathleen M CM Brennan Jennifer J Brouillet Jeremy Jean JJ Carr Adrian A Cheung Ming-Sin MS Clawson Hiram H Contrino Sergio S Dannenberg Luke O LO Dernburg Abby F AF Desai Arshad A Dick Lindsay L Dosé Andréa C AC Du Jiang J Egelhofer Thea T Ercan Sevinc S Euskirchen Ghia G Ewing Brent B Feingold Elise A EA Gassmann Reto R Good Peter J PJ Green Phil P Gullier Francois F Gutwein Michelle M Guyer Mark S MS Habegger Lukas L Han Ting T Henikoff Jorja G JG Henz Stefan R SR Hinrichs Angie A Holster Heather H Hyman Tony T Iniguez A Leo AL Janette Judith J Jensen Morten M Kato Masaomi M Kent W James WJ Kephart Ellen E Khivansara Vishal V Khurana Ekta E Kim John K JK Kolasinska-Zwierz Paulina P Lai Eric C EC Latorre Isabel I Leahey Amber A Lewis Suzanna S Lloyd Paul P Lochovsky Lucas L Lowdon Rebecca F RF Lubling Yaniv Y Lyne Rachel R MacCoss Michael M Mackowiak Sebastian D SD Mangone Marco M McKay Sheldon S Mecenas Desirea D Merrihew Gennifer G Miller David M DM Muroyama Andrew A Murray John I JI Ooi Siew-Loon SL Pham Hoang H Phippen Taryn T Preston Elicia A EA Rajewsky Nikolaus N Rätsch Gunnar G Rosenbaum Heidi H Rozowsky Joel J Rutherford Kim K Ruzanov Peter P Sarov Mihail M Sasidharan Rajkumar R Sboner Andrea A Scheid Paul P Segal Eran E Shin Hyunjin H Shou Chong C Slack Frank J FJ Slightam Cindie C Smith Richard R Spencer William C WC Stinson E O EO Taing Scott S Takasaki Teruaki T Vafeados Dionne D Voronina Ksenia K Wang Guilin G Washington Nicole L NL Whittle Christina M CM Wu Beijing B Yan Koon-Kiu KK Zeller Georg G Zha Zheng Z Zhong Mei M Zhou Xingliang X Ahringer Julie J Strome Susan S Gunsalus Kristin C KC Micklem Gos G Liu X Shirley XS Reinke Valerie V Kim Stuart K SK Hillier LaDeana W LW Henikoff Steven S Piano Fabio F Snyder Michael M Stein Lincoln L Lieb Jason D JD Waterston Robert H RH

Science (New York, N.Y.) 20101222 6012

We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor-binding sites, and maps of chromatin organization. From this, we created more complete and accurate gene models, including alternative splice forms and candidate noncoding RNAs. We constructed hierarchical networks of trans ...[more]

PMID: 21177976

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Project description:FoxO transcription factors promote longevity across taxa. How they do so is poorly understood. In the nematode Caenorhabditis elegans, the A- and F-isoforms of the FoxO transcription factor DAF-16 extend life span in the context of reduced DAF-2 insulin-like growth factor receptor (IGFR) signaling. To elucidate the mechanistic basis for DAF-16/FoxO-dependent life span extension, we performed an integrative analysis of isoform-specific daf-16/FoxO mutants. In contrast to previous studies suggesting that DAF-16F plays a more prominent role in life span control than DAF-16A, isoform-specific daf-16/FoxO mutant phenotypes and whole transcriptome profiling revealed a predominant role for DAF-16A over DAF-16F in life span control, stress resistance, and target gene regulation. Integration of these datasets enabled the prioritization of a subset of 92 DAF-16/FoxO target genes for functional interrogation. Among 29 genes tested, two DAF-16A-specific target genes significantly influenced longevity. A loss-of-function mutation in the conserved gene gst-20, which is induced by DAF-16A, reduced life span extension in the context of daf-2/IGFR RNAi without influencing longevity in animals subjected to control RNAi. Therefore, gst-20 promotes DAF-16/FoxO-dependent longevity. Conversely, a loss-of-function mutation in srr-4, a gene encoding a seven-transmembrane-domain receptor family member that is repressed by DAF-16A, extended life span in control animals, indicating that DAF-16/FoxO may extend life span at least in part by reducing srr-4 expression. Our discovery of new longevity genes underscores the efficacy of our integrative strategy while providing a general framework for identifying specific downstream gene regulatory events that contribute substantially to transcription factor functions. As FoxO transcription factors have conserved functions in promoting longevity and may be dysregulated in aging-related diseases, these findings promise to illuminate fundamental principles underlying aging in animals.

Dataset Information

Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project.

Publications

Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project.

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