title: Sex- and tissue-specific functions of Drosophila doublesex transcription factor target genes.
abstract: Primary sex-determination "switches" evolve rapidly, but Doublesex (DSX)-related transcription factors (DMRTs) act downstream of these switches to control sexual development in most animal species. Drosophila dsx encodes female- and male-specific isoforms (DSX(F) and DSX(M)), but little is known about how dsx controls sexual development, whether DSX(F) and DSX(M) bind different targets, or how DSX proteins direct different outcomes in diverse tissues. We undertook genome-wide analyses to identify DSX targets using in vivo occupancy, binding site prediction, and evolutionary conservation. We find that DSX(F) and DSX(M) bind thousands of the same targets in multiple tissues in both sexes, yet these targets have sex- and tissue-specific functions. Interestingly, DSX targets show considerable overlap with targets identified for mouse DMRT1. DSX targets include transcription factors and signaling pathway components providing for direct and indirect regulation of sex-biased expression.
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Clough
authors.affiliation: Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Jimenez
authors.affiliation: Computational Biology Branch, NCBI, NLM, NIH, Bethesda, MD 20814, USA.
authors.forename: Yoo-Ah
authors.initials: YA
authors.lastname: Kim
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA; Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA. Electronic address: cale.whitworth@nih.gov.
authors.forename: Cale
authors.initials: C
authors.lastname: Whitworth
authors.affiliation: Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3PT, UK.
authors.forename: Megan C
authors.initials: MC
authors.lastname: Neville
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Leonie U
authors.initials: LU
authors.lastname: Hempel
authors.affiliation: Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3PT, UK.
authors.forename: Hania J
authors.initials: HJ
authors.lastname: Pavlou
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Zhen-Xia
authors.initials: ZX
authors.lastname: Chen
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sturgill
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Ryan K
authors.initials: RK
authors.lastname: Dale
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Harold E
authors.initials: HE
authors.lastname: Smith
authors.affiliation: Computational Biology Branch, NCBI, NLM, NIH, Bethesda, MD 20814, USA.
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Przytycka
authors.affiliation: Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3PT, UK.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Goodwin
authors.affiliation: Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Van Doren
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Oliver
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D055106:Genome-Wide Association Study; D008297:Male; D051379:Mice; D010641:Phenotype; D034622:RNA Interference; D017422:Sequence Analysis, DNA; D012737:Sex Factors; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C110547:DMRT1 protein; D004268:DNA-Binding Proteins; C070369:DSX protein, Drosophila; D029721:Drosophila Proteins; D014157:Transcription Factors