title: Functional cis-regulatory modules encoded by mouse-specific endogenous retrovirus.
abstract: Cis-regulatory modules contain multiple transcription factor (TF)-binding sites and integrate the effects of each TF to control gene expression in specific cellular contexts. Transposable elements (TEs) are uniquely equipped to deposit their regulatory sequences across a genome, which could also contain cis-regulatory modules that coordinate the control of multiple genes with the same regulatory logic. We provide the first evidence of mouse-specific TEs that encode a module of TF-binding sites in mouse embryonic stem cells (ESCs). The majority (77%) of the individual TEs tested exhibited enhancer activity in mouse ESCs. By mutating individual TF-binding sites within the TE, we identified a module of TF-binding motifs that cooperatively enhanced gene expression. Interestingly, we also observed the same motif module in the in silico constructed ancestral TE that also acted cooperatively to enhance gene expression. Our results suggest that ancestral TE insertions might have brought in cis-regulatory modules into the mouse genome.
authors.affiliation: Division of Biological and Biomedical Sciences, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, Missouri 63110, USA.|Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, 4515 McKinley Avenue, St. Louis, Missouri 63110, USA.
authors.forename: Vasavi
authors.initials: V
authors.lastname: Sundaram
authors.affiliation: Division of Biological and Biomedical Sciences, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, Missouri 63110, USA.|Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, 4515 McKinley Avenue, St. Louis, Missouri 63110, USA.
authors.forename: Mayank N K
authors.initials: MN
authors.lastname: Choudhary
authors.affiliation: Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, 4515 McKinley Avenue, St. Louis, Missouri 63110, USA.
authors.forename: Erica
authors.initials: E
authors.lastname: Pehrsson
authors.affiliation: Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, 4515 McKinley Avenue, St. Louis, Missouri 63110, USA.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Xing
authors.affiliation: Division of Biological and Biomedical Sciences, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, Missouri 63110, USA.|Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, 4515 McKinley Avenue, St. Louis, Missouri 63110, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Fiore
authors.affiliation: Division of Biological and Biomedical Sciences, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, Missouri 63110, USA.|Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, 4515 McKinley Avenue, St. Louis, Missouri 63110, USA.
authors.forename: Manishi
authors.initials: M
authors.lastname: Pandey
authors.affiliation: Division of Biological and Biomedical Sciences, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, Missouri 63110, USA.|Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, 4515 McKinley Avenue, St. Louis, Missouri 63110, USA.
authors.forename: Brett
authors.initials: B
authors.lastname: Maricque
authors.affiliation: Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, 4515 McKinley Avenue, St. Louis, Missouri 63110, USA.
authors.forename: Methma
authors.initials: M
authors.lastname: Udawatta
authors.affiliation: Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, 4515 McKinley Avenue, St. Louis, Missouri 63110, USA.
authors.forename: Duc
authors.initials: D
authors.lastname: Ngo
authors.affiliation: Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, 4515 McKinley Avenue, St. Louis, Missouri 63110, USA.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, 4515 McKinley Avenue, St. Louis, Missouri 63110, USA.
authors.forename: Asia
authors.initials: A
authors.lastname: Paguntalan
authors.affiliation: Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, 4515 McKinley Avenue, St. Louis, Missouri 63110, USA.
authors.forename: Tammy
authors.initials: T
authors.lastname: Ray
authors.affiliation: Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, 4515 McKinley Avenue, St. Louis, Missouri 63110, USA.
authors.forename: Ava
authors.initials: A
authors.lastname: Hughes
authors.affiliation: Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, 4515 McKinley Avenue, St. Louis, Missouri 63110, USA.
authors.forename: Barak A
authors.initials: BA
authors.lastname: Cohen
authors.affiliation: Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, 4515 McKinley Avenue, St. Louis, Missouri 63110, USA.
authors.forename: Ting
authors.identifier: 0000-0002-6800-242X
authors.initials: T
authors.lastname: Wang
mesh_terms: D000818:Animals; D004251:DNA Transposable Elements / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000378:metabolism*; D019143:Evolution, Molecular; D015971:Gene Expression Regulation, Enzymologic; D016678:Genome; D051379:Mice; D020079:Terminal Repeat Sequences; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004251:DNA Transposable Elements; D014157:Transcription Factors