Genome-wide comparative analysis reveals human-mouse regulatory landscape and evolution

• Type of Material: Article
• Authors: Olgert Denas, Emory University; Richard Sandstrom, University of Washington; Yong Cheng, Stanford University; Kathryn Beal, European Bioinformat Inst EMBL EBI; Javier Herrero, The Genome Analysis Centre; Ross C. Hardison, Pennsylvania State University; James Taylor, Emory University
• Language: English
• Date: 2015-02-14
• Publisher: BMC
• Publication Version: Final Published Version
• Copyright Statement: Copyright © Denas et al.; licensee BioMed Central. 2015
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s12864-015-1245-6
• Title of Journal or Parent Work: BMC Genomics
• Volume: 16
• Issue: 1
• Start Page: 87
• End Page: 87
• Grant/Funding Information: This project was supported by grants from the National Institutes of Health to RCH and JT, specifically American Recovery and Reinvestment Act (ARRA) funds through grant number RC2 HG005573 from the National Human Genome Research Institute, and grants with numbers R01 DK065806 and R56 DK065806 from the National Institute for Diabetes, Digestive, and Kidney Diseases.; This work was also supported by the Wellcome Trust (grant number 095908) and the European Molecular Biology Laboratory.
• Keywords: NATURAL-SELECTION; Comparative genomics; Life Sciences & Biomedicine; Genetics & Heredity; DNA ELEMENTS; Science & Technology; Mouse ENCODE; BINDING; TRANSCRIPTION; GENE; ENCYCLOPEDIA; Biotechnology & Applied Microbiology; Regulatory sequences
• Research Categories: Biology, Microbiology; Biology, Genetics

Abstract

Background: Because species-specific gene expression is driven by species-specific regulation, understanding the relationship between sequence and function of the regulatory regions in different species will help elucidate how differences among species arise. Despite active experimental and computational research, relationships among sequence, conservation, and function are still poorly understood. Results: We compared transcription factor occupied segments (TFos) for 116 human and 35 mouse TFs in 546 human and 125 mouse cell types and tissues from the Human and the Mouse ENCODE projects. We based the map between human and mouse TFos on a one-to-one nucleotide cross-species mapper, bnMapper, that utilizes whole genome alignments (WGA). Conclusion: We mapped regulatory sequences from an extensive number of TFs and cell types between human and mouse using WGA. A comparative analysis of this correspondence unveiled the extent of the shared regulatory sequence across TFs and cell types under study. Importantly, a large part of the shared regulatory sequence is repurposed on the other species. This sequence, fueled by turnover events, provides a strong case for exaptation in regulatory elements.