Comparative analysis of regulatory information and circuits across distant species

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 regul...

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Main Authors: Kheradpour, Pouya, Kundaje, Anshul, Wu, Yi-Chieh, Kellis, Manolis
Other Authors: Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Format: Article
Language:en_US
Published: American Association for the Advancement of Science (AAAS) 2016
Online Access:http://hdl.handle.net/1721.1/100768
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author Kheradpour, Pouya
Kundaje, Anshul
Wu, Yi-Chieh
Kellis, Manolis
author2 Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
author_facet Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Kheradpour, Pouya
Kundaje, Anshul
Wu, Yi-Chieh
Kellis, Manolis
author_sort Kheradpour, Pouya
collection MIT
description 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.
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spelling mit-1721.1/1007682022-09-30T17:44:47Z Comparative analysis of regulatory information and circuits across distant species Kheradpour, Pouya Kundaje, Anshul Wu, Yi-Chieh Kellis, Manolis Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Kheradpour, Pouya Kundaje, Anshul Wu, Yi-Chieh Kellis, Manolis 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. 2016-01-08T01:47:46Z 2016-01-08T01:47:46Z 2014-08 2013-11 Article http://purl.org/eprint/type/JournalArticle 0028-0836 1476-4687 http://hdl.handle.net/1721.1/100768 Boyle, Alan P., Carlos L. Araya, Cathleen Brdlik, Philip Cayting, Chao Cheng, Yong Cheng, Kathryn Gardner, et al. “Comparative Analysis of Regulatory Information and Circuits Across Distant Species.” Nature 512, no. 7515 (August 27, 2014): 453–456. en_US http://dx.doi.org/10.1038/nature13668 Nature Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for the Advancement of Science (AAAS) PMC
spellingShingle Kheradpour, Pouya
Kundaje, Anshul
Wu, Yi-Chieh
Kellis, Manolis
Comparative analysis of regulatory information and circuits across distant species
title Comparative analysis of regulatory information and circuits across distant species
title_full Comparative analysis of regulatory information and circuits across distant species
title_fullStr Comparative analysis of regulatory information and circuits across distant species
title_full_unstemmed Comparative analysis of regulatory information and circuits across distant species
title_short Comparative analysis of regulatory information and circuits across distant species
title_sort comparative analysis of regulatory information and circuits across distant species
url http://hdl.handle.net/1721.1/100768
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