title: 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. Single nucleotide variants at sites with potential regulatory functions are enriched in occupancy-conserved TF-occupied sequences.
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Program in Bioinformatics and Integrative Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Bong-Hyun
authors.initials: BH
authors.lastname: Kim
authors.affiliation: Center for Comparative Genomics and Bioinformatics, Huck Institutes of the Life Sciences, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Weisheng
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Cayting
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Alan P
authors.initials: AP
authors.lastname: Boyle
authors.affiliation: Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA.
authors.forename: Vasavi
authors.initials: V
authors.lastname: Sundaram
authors.affiliation: Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Xing
authors.affiliation: Center for Comparative Genomics and Bioinformatics, Huck Institutes of the Life Sciences, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Nergiz
authors.initials: N
authors.lastname: Dogan
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Ghia
authors.initials: G
authors.lastname: Euskirchen
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA.|Division of Cardiovascular Medicine, Stanford University, Stanford, CA 94304, USA.
authors.forename: Shin
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA.|Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Yiing
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Lawrence Berkeley National Laboratory, Genomics Division, Berkeley, CA 94701,USA.|Department of Energy Joint Genome Institute, Walnut Creek, CA 94598, USA.|School of Natural Sciences, University of California, Merced, CA 95343,USA.
authors.forename: Axel
authors.initials: A
authors.lastname: Visel
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Trupti
authors.initials: T
authors.lastname: Kawli
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Xinqiong
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Dorrelyn
authors.initials: D
authors.lastname: Patacsil
authors.affiliation: Center for Comparative Genomics and Bioinformatics, Huck Institutes of the Life Sciences, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Keller
authors.affiliation: Center for Comparative Genomics and Bioinformatics, Huck Institutes of the Life Sciences, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Belinda
authors.initials: B
authors.lastname: Giardine
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Anshul
authors.initials: A
authors.lastname: Kundaje
authors.affiliation: Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Lawrence Berkeley National Laboratory, Genomics Division, Berkeley, CA 94701,USA.|Department of Energy Joint Genome Institute, Walnut Creek, CA 94598, USA.
authors.forename: Len A
authors.initials: LA
authors.lastname: Pennacchio
authors.affiliation: Program in Bioinformatics and Integrative Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Weng
authors.affiliation: Center for Comparative Genomics and Bioinformatics, Huck Institutes of the Life Sciences, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Ross C
authors.initials: RC
authors.lastname: Hardison
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Snyder
mesh_terms: D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D017124:Conserved Sequence / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D016678:Genome / Q000235:genetics*; D023281:Genomics; D006801:Humans; D051379:Mice; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D002843:Chromatin; D014157:Transcription Factors