Principles of regulatory information conservation between mouse and human
Program in Bioinformatics and Integrative Biology; Department of Biochemistry and Molecular Pharmacology
Animals; Cell Line; Chromatin; Conserved Sequence; Enhancer Elements, Genetic; Genome; *Genomics; Humans; Mice; Polymorphism, Single Nucleotide; Regulatory Sequences, Nucleic Acid; Transcription Factors
Biochemistry, Biophysics, and Structural Biology | Bioinformatics | Computational Biology | Integrative Biology | Systems Biology
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.
DOI of Published Version
Nature. 2014 Nov 20;515(7527):371-5. doi: 10.1038/nature13985. Link to article on publisher's site
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" (2014). Program in Bioinformatics and Integrative Biology Publications and Presentations. 51.