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Title: Principles of regulatory information conservation between mouse and human

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:
 [1] ;  [1] ;  [2] ;  [3] ;  [1] ;  [1] ;  [4] ;  [4] ;  [5] ;  [1] ;  [1] ;  [1] ;  [6] ;  [7] ;  [1] ;  [1] ;  [1] ;  [5] ;  [5] ;  [1] more »;  [4] ;  [8] ;  [2] ;  [5] ;  [1] « less
  1. Stanford Univ., Stanford, CA (United States)
  2. Univ. of Massachusetts Medical School, Worcester, MA (United States)
  3. Pennsylvania State Univ., University Park, PA (United States); Univ. of Michigan, Ann Arbor, MI (United States)
  4. Washington Univ. School of Medicine, St. Louis, MO (United States)
  5. Pennsylvania State Univ., University Park, PA (United States)
  6. Stanford Univ., Stanford, CA (United States); Washington Univ. School of Medicine, St. Louis, MO (United States)
  7. 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)
  8. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); DOE Joint Genome Institute, Walnut Creek, CA (United States)
Publication Date:
OSTI Identifier:
1257363
Grant/Contract Number:
AC02-05CH11231
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
Research Org:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Org:
USDOE
Contributing Orgs:
The Mouse ENCODE Consortium
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES