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, Anshul KundajeTing Wang, Len A. Pennacchio, Zhiping Weng, Ross C. Hardison, Michael P. Snyder

Research output: Contribution to journalArticle

146 Scopus citations

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.

Original languageEnglish
Pages (from-to)371-375
Number of pages5
JournalNature
Volume515
Issue number7527
DOIs
StatePublished - Nov 20 2014

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    Cheng, Y., Ma, Z., Kim, B. H., Wu, W., Cayting, P., Boyle, A. P., Sundaram, V., Xing, X., Dogan, N., Li, J., Euskirchen, G., Lin, S., Lin, Y., Visel, A., Kawli, T., Yang, X., Patacsil, D., Keller, C. A., Giardine, B., ... Snyder, M. P. (2014). Principles of regulatory information conservation between mouse and human. Nature, 515(7527), 371-375. https://doi.org/10.1038/nature13985