title: Genome-wide identification of regulatory elements in Sertoli cells.
abstract: A current goal of molecular biology is to identify transcriptional networks that regulate cell differentiation. However, identifying functional gene regulatory elements has been challenging in the context of developing tissues where material is limited and cell types are mixed. To identify regulatory sites during sex determination, we subjected Sertoli cells from mouse fetal testes to DNaseI-seq and ChIP-seq for H3K27ac. DNaseI-seq identified putative regulatory sites around genes enriched in Sertoli and pregranulosa cells; however, active enhancers marked by H3K27ac were enriched proximal to only Sertoli-enriched genes. Sequence analysis identified putative binding sites of known and novel transcription factors likely controlling Sertoli cell differentiation. As a validation of this approach, we identified a novel Sertoli cell enhancer upstream ofWt1, and used it to drive expression of a transgenic reporter in Sertoli cells. This work furthers our understanding of the complex genetic network that underlies sex determination and identifies regions that potentially harbor non-coding mutations underlying disorders of sexual development.
authors.affiliation: Department of Cell Biology, Duke University, Durham, NC 27710, USA.|Department of Obstetrics and Gynecology, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Danielle M
authors.identifier: 0000-0002-4303-1187
authors.initials: DM
authors.lastname: Maatouk
authors.affiliation: Program in Computational Biology and Bioinformatics, Duke University, Durham, NC 27708, USA.
authors.forename: Anirudh
authors.initials: A
authors.lastname: Natarajan
authors.affiliation: Center for Genomic and Computational Biology, Duke University, Durham, NC 27708, USA.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Shibata
authors.affiliation: Center for Genomic and Computational Biology, Duke University, Durham, NC 27708, USA.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Song
authors.affiliation: Center for Genomic and Computational Biology, Duke University, Durham, NC 27708, USA.|Department of Pediatrics, Division of Medical Genetics, Duke University, Durham, NC 27708, USA.
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Crawford
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University, Durham, NC 27708, USA.|Max Delbruck Center for Molecular Medicine, Berlin 13125, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Ohler
authors.affiliation: Department of Cell Biology, Duke University, Durham, NC 27710, USA blanche.capel@duke.edu.
authors.forename: Blanche
authors.identifier: 0000-0002-6587-0969
authors.initials: B
authors.lastname: Capel
mesh_terms: D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D003850:Deoxyribonuclease I / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D017930:Genes, Reporter; D016678:Genome; D006657:Histones / Q000378:metabolism; D006720:Homozygote; D008297:Male; D051379:Mice; D009154:Mutation; D011401:Promoter Regions, Genetic; D050436:Regulatory Elements, Transcriptional; D012708:Sertoli Cells / Q000378:metabolism*; D019849:Sex Determination Processes; D013737:Testis / Q000196:embryology; D019076:Transgenes
chemical_list: D006657:Histones; D003850:Deoxyribonuclease I
keywords: Genome-wide enhancer profiling; Mouse; Sertoli cell development; Sex determination