Comparative analysis of regulatory information and circuits across distant species

Alan P. Boyle, Carlos L. Araya, Cathleen Brdlik, Philip Cayting, Chao Cheng, Yong Cheng, Kathryn Gardner, Ladeana W. Hillier, Judith Janette, Lixia Jiang, Dionna Kasper, Trupti Kawli, Pouya Kheradpour, Anshul Kundaje, Jingyi Jessica Li, Lijia Ma, Wei Niu, E. Jay Rehm, Joel Rozowsky, Matthew SlatteryRebecca Spokony, Robert Terrell, Dionne Vafeados, Daifeng Wang, Peter Weisdepp, Yi Chieh Wu, Dan Xie, Koon Kiu Yan, Elise A. Feingold, Peter J. Good, Michael J. Pazin, Haiyan Huang, Peter J. Bickel, Steven E. Brenner, Valerie Reinke, Robert H. Waterston, Mark Gerstein, Kevin P. White, Manolis Kellis, Michael Snyder

Research output: Contribution to journalArticlepeer-review

130 Scopus citations


Despite the large evolutionary distances between metazoan species, they can show remarkable commonalities in their biology, and this has helped to establish fly and worm as model organisms for human biology. Although studies of individual elements and factors have explored similarities in gene regulation, a large-scale comparative analysis of basic principles of transcriptional regulatory features is lacking. Here we map the genome-wide binding locations of 165 human, 93 worm and 52 fly transcription regulatory factors, generating a total of 1,019 data sets from diverse cell types, developmental stages, or conditions in the three species, of which 498 (48.9%) are presented here for the first time. We find that structural properties of regulatory networks are remarkably conserved and that orthologous regulatory factor families recognize similar binding motifs in vivo and show some similar co-associations. Our results suggest that gene-regulatory properties previously observed for individual factors are general principles of metazoan regulation that are remarkably well-preserved despite extensive functional divergence of individual network connections. The comparative maps of regulatory circuitry provided here will drive an improved understanding of the regulatory underpinnings of model organism biology and how these relate to human biology, development and disease.

Original languageEnglish (US)
Pages (from-to)453-456
Number of pages4
Issue number7515
StatePublished - Aug 28 2014

Bibliographical note

Funding Information:
Acknowledgements This work is supported by the NHGRI as part of the modENCODE and ENCODE projects. This work was funded by U01HG004264, RC2HG005679 and P50GM081892 to K.P.W., U54HG006996, U54HG004558 and U01HG004267 to M.S., and F32GM101778 to K.E.G.


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