Principles of regulatory information conservation between mouse and human
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. Lastly, single nucleotide variants at sites with potential regulatory functions are enriched in occupancy-conserved TF-occupied sequences.
- Authors:
-
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- Stanford Univ., Stanford, CA (United States)
- Univ. of Massachusetts Medical School, Worcester, MA (United States)
- Pennsylvania State Univ., University Park, PA (United States); Univ. of Michigan, Ann Arbor, MI (United States)
- Washington Univ. School of Medicine, St. Louis, MO (United States)
- Pennsylvania State Univ., University Park, PA (United States)
- Stanford Univ., Stanford, CA (United States); Washington Univ. School of Medicine, St. Louis, MO (United States)
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); DOE Joint Genome Institute, Walnut Creek, CA (United States); Univ. of California, Merced, CA (United States)
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); DOE Joint Genome Institute, Walnut Creek, CA (United States)
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE
- Contributing Org.:
- The Mouse ENCODE Consortium
- OSTI Identifier:
- 1257363
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature (London)
- Additional Journal Information:
- Journal Name: Nature (London); Journal Volume: 515; Journal Issue: 7527; Journal ID: ISSN 0028-0836
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES
Citation Formats
Cheng, Yong, Ma, Zhihai, Kim, Bong-Hyun, Wu, Weisheng, Cayting, Philip, Boyle, Alan P., Sundaram, Vasavi, Xing, Xiaoyun, Dogan, Nergiz, Li, Jingjing, Euskirchen, Ghia, Lin, Shin, Lin, Yiing, Visel, Axel, Kawli, Trupti, Yang, Xinqiong, Patacsil, Dorrelyn, Keller, Cheryl A., Giardine, Belinda, Kundaje, Anshul, Wang, Ting, Pennacchio, Len A., Weng, Zhiping, Hardison, Ross C., and Snyder, Michael P. Principles of regulatory information conservation between mouse and human. United States: N. p., 2014.
Web. doi:10.1038/nature13985.
Cheng, Yong, Ma, Zhihai, Kim, Bong-Hyun, Wu, Weisheng, Cayting, Philip, Boyle, Alan P., Sundaram, Vasavi, Xing, Xiaoyun, Dogan, Nergiz, Li, Jingjing, Euskirchen, Ghia, Lin, Shin, Lin, Yiing, Visel, Axel, Kawli, Trupti, Yang, Xinqiong, Patacsil, Dorrelyn, Keller, Cheryl A., Giardine, Belinda, Kundaje, Anshul, Wang, Ting, Pennacchio, Len A., Weng, Zhiping, Hardison, Ross C., & Snyder, Michael P. Principles of regulatory information conservation between mouse and human. United States. https://doi.org/10.1038/nature13985
Cheng, Yong, Ma, Zhihai, Kim, Bong-Hyun, Wu, Weisheng, Cayting, Philip, Boyle, Alan P., Sundaram, Vasavi, Xing, Xiaoyun, Dogan, Nergiz, Li, Jingjing, Euskirchen, Ghia, Lin, Shin, Lin, Yiing, Visel, Axel, Kawli, Trupti, Yang, Xinqiong, Patacsil, Dorrelyn, Keller, Cheryl A., Giardine, Belinda, Kundaje, Anshul, Wang, Ting, Pennacchio, Len A., Weng, Zhiping, Hardison, Ross C., and Snyder, Michael P. Wed .
"Principles of regulatory information conservation between mouse and human". United States. https://doi.org/10.1038/nature13985. https://www.osti.gov/servlets/purl/1257363.
@article{osti_1257363,
title = {Principles of regulatory information conservation between mouse and human},
author = {Cheng, Yong and Ma, Zhihai and Kim, Bong-Hyun and Wu, Weisheng and Cayting, Philip and Boyle, Alan P. and Sundaram, Vasavi and Xing, Xiaoyun and Dogan, Nergiz and Li, Jingjing and Euskirchen, Ghia and Lin, Shin and Lin, Yiing and Visel, Axel and Kawli, Trupti and Yang, Xinqiong and Patacsil, Dorrelyn and Keller, Cheryl A. and Giardine, Belinda and Kundaje, Anshul and Wang, Ting and Pennacchio, Len A. and Weng, Zhiping and Hardison, Ross C. and Snyder, Michael P.},
abstractNote = {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. Lastly, single nucleotide variants at sites with potential regulatory functions are enriched in occupancy-conserved TF-occupied sequences.},
doi = {10.1038/nature13985},
journal = {Nature (London)},
number = 7527,
volume = 515,
place = {United States},
year = {Wed Nov 19 00:00:00 EST 2014},
month = {Wed Nov 19 00:00:00 EST 2014}
}
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