Principles of regulatory information conservation between mouse and human

Yong Cheng, Zhihai Ma, Bong-Hyun Kim, Weisheng Wu, Philip Cayting, Alan P. Boyle, Vasavi Sundaram, Xiaoyun Xing, Nergiz Dogan, Jingjing Li, Ghia Euskirchen, Shin Lin, Yiing Lin, Axel Visel, Trupti Kawli, Xinqiong Yang, Dorrelyn Patacsil, Cheryl A. Keller, Belinda Giardine, The Mouse ENCODE Consortium, Anshul Kundaje, Ting Wang, Len A. Pennacchio, Zhiping Weng, Ross C. Hardison () and Michael P. Snyder ()
Additional contact information
Yong Cheng: Stanford University
Zhihai Ma: Stanford University
Bong-Hyun Kim: Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School
Weisheng Wu: Center for Comparative Genomics and Bioinformatics, Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park
Philip Cayting: Stanford University
Alan P. Boyle: Stanford University
Vasavi Sundaram: Center for Genome Sciences and Systems Biology, Washington University School of Medicine
Xiaoyun Xing: Center for Genome Sciences and Systems Biology, Washington University School of Medicine
Nergiz Dogan: Center for Comparative Genomics and Bioinformatics, Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park
Jingjing Li: Stanford University
Ghia Euskirchen: Stanford University
Shin Lin: Stanford University
Yiing Lin: Stanford University
Axel Visel: Lawrence Berkeley National Laboratory
Trupti Kawli: Stanford University
Xinqiong Yang: Stanford University
Dorrelyn Patacsil: Stanford University
Cheryl A. Keller: Center for Comparative Genomics and Bioinformatics, Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park
Belinda Giardine: Center for Comparative Genomics and Bioinformatics, Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park
Anshul Kundaje: Stanford University
Ting Wang: Center for Genome Sciences and Systems Biology, Washington University School of Medicine
Len A. Pennacchio: Lawrence Berkeley National Laboratory
Zhiping Weng: Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School
Ross C. Hardison: Center for Comparative Genomics and Bioinformatics, Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park
Michael P. Snyder: Stanford University

Nature, 2014, vol. 515, issue 7527, 371-375

Abstract: Abstract To broaden our understanding of the evolution of gene regulation mechanisms, we generated occupancy profiles for 34 orthologous transcription factors (TFs) in human–mouse erythroid progenitor, lymphoblast and embryonic stem-cell lines. By combining the genome-wide transcription factor occupancy repertoires, associated epigenetic signals, and co-association patterns, here we deduce several evolutionary principles of gene regulatory features operating since the mouse and human lineages diverged. The genomic distribution profiles, primary binding motifs, chromatin states, and DNA methylation preferences are well conserved for TF-occupied sequences. However, the extent to which orthologous DNA segments are bound by orthologous TFs varies both among TFs and with genomic location: binding at promoters is more highly conserved than binding at distal elements. Notably, occupancy-conserved TF-occupied sequences tend to be pleiotropic; they function in several tissues and also co-associate with many TFs. Single nucleotide variants at sites with potential regulatory functions are enriched in occupancy-conserved TF-occupied sequences.

Date: 2014
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DOI: 10.1038/nature13985

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