Principles of regulatory information conservation between mouse and human

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., Kundaje, A., Wang, T., Pennacchio, L. A., Weng, Z., Hardison, R. C., Snyder, M. P., Consortium, Mouse ENCODE (2014) Principles of regulatory information conservation between mouse and human. Nature, 515 (7527). pp. 371-5. ISSN 0028-0836

URL: http://www.ncbi.nlm.nih.gov/pubmed/25409826
DOI: 10.1038/nature13985

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.

Item Type: Paper
Uncontrolled Keywords: Animals Cell Line Chromatin/genetics/metabolism Conserved Sequence/*genetics Enhancer Elements, Genetic/genetics Genome/*genetics *Genomics Humans Mice Polymorphism, Single Nucleotide/genetics Regulatory Sequences, Nucleic Acid/*genetics Transcription Factors/*metabolism
Subjects: bioinformatics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Chromatin dynamics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > genomes
organism description > animal > mammal > primates > hominids > human
organism description > animal > mammal > rodent > mouse
Investigative techniques and equipment > assays > whole genome sequencing
CSHL Authors:
Communities: CSHL Cancer Center Program > Gene Regulation and Cell Proliferation
CSHL labs > Gingeras lab
Depositing User: Matt Covey
Date Deposited: 06 Oct 2015 20:04
Last Modified: 06 Oct 2015 20:04
PMCID: PMC4343047
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31915

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