title: TRA-1 ChIP-seq reveals regulators of sexual differentiation and multilevel feedback in nematode sex determination.
abstract: How sexual regulators translate global sexual fate into appropriate local sexual differentiation events is perhaps the least understood aspect of sexual development. Here we have used ChIP followed by deep sequencing (ChIP-seq) to identify direct targets of the nematode global sexual regulator Transformer 1 (TRA-1), a transcription factor acting at the interface between organism-wide and cell-specific sexual regulation to control all sex-specific somatic differentiation events. We identified 184 TRA-1-binding sites in Caenorhabditis elegans, many with temporal- and/or tissue-specific TRA-1 association. We also identified 78 TRA-1-binding sites in the related nematode Caenorhabditis briggsae, 19 of which are conserved between the two species. Some DNA segments containing TRA-1-binding sites drive male-specific expression patterns, and RNAi depletion of some genes adjacent to TRA-1-binding sites results in defects in male sexual development. TRA-1 binds to sites adjacent to a number of heterochronic regulatory genes, some of which drive male-specific expression, suggesting that TRA-1 imposes sex specificity on developmental timing. We also found evidence for TRA-1 feedback regulation of the global sex-determination pathway: TRA-1 binds its own locus and those of multiple upstream masculinizing genes, and most of these associations are conserved in C. briggsae. Thus, TRA-1 coordinates sexual development by reinforcing the sex-determination decision and directing downstream sexual differentiation events.
authors.affiliation: Department of Genetics, Cell Biology, and Development and Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Matt
authors.initials: M
authors.lastname: Berkseth
authors.forename: Kohta
authors.initials: K
authors.lastname: Ikegami
authors.forename: Swathi
authors.initials: S
authors.lastname: Arur
authors.forename: Jason D
authors.initials: JD
authors.lastname: Lieb
authors.forename: David
authors.initials: D
authors.lastname: Zarkower
mesh_terms: D000818:Animals; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D025461:Feedback, Physiological / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D008297:Male; D034622:RNA Interference; D017422:Sequence Analysis, DNA; D019849:Sex Determination Processes / Q000235:genetics / Q000502:physiology*; D012733:Sex Differentiation / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C121025:tra-1 protein, C elegans
references.citation: Nat Genet. 2001 Aug;28(4):327-34
references.pmid: 11455386
references.citation: Development. 1997 Jun;124(11):2191-201
references.pmid: 9187145
references.citation: Gene. 1990 Sep 14;93(2):189-98
references.pmid: 2121610
references.citation: Genes Dev. 1988 May;2(5):606-16
references.pmid: 3384333
references.citation: Cell. 1992 Jul 24;70(2):237-49
references.pmid: 1339311
references.citation: Genetics. 1993 Mar;133(3):543-60
references.pmid: 8384144
references.citation: Genetics. 1988 Oct;120(2):435-52
references.pmid: 3197956
references.citation: Genes Dev. 2007 Dec 1;21(23):3195-207
references.pmid: 18056429
references.citation: Dev Cell. 2011 May 17;20(5):677-88
references.pmid: 21571224
references.citation: Dev Biol. 1977 Mar;56(1):110-56
references.pmid: 838129
references.citation: Development. 1992 Nov;116(3):755-66
references.pmid: 1289064
references.citation: PLoS One. 2009;4(3):e4625
references.pmid: 19259264
references.citation: Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):18022-7
references.pmid: 20921392
references.citation: Dev Biol. 1981 Oct 30;87(2):286-300
references.pmid: 7286433
references.citation: Dev Biol. 2001 Jan 15;229(2):537-53
references.pmid: 11150246
references.citation: Development. 2009 Dec;136(23):3881-7
references.pmid: 19906855
references.citation: Nature. 1983 Jul 21-27;304(5923):267-8
references.pmid: 6866126
references.citation: Development. 2000 Oct;127(20):4469-80
references.pmid: 11003845
references.citation: Cell. 1999 Aug 6;98(3):317-27
references.pmid: 10458607
references.citation: Genetics. 1996 Oct;144(2):587-95
references.pmid: 8889522
references.citation: EMBO J. 1991 Jan;10(1):171-6
references.pmid: 1703488
references.citation: Nature. 1992 Feb 6;355(6360):551-5
references.pmid: 1741033
references.citation: Nature. 1997 Dec 4;390(6659):477-84
references.pmid: 9393998
references.citation: Genes Dev. 2004 May 15;18(10):1198-208
references.pmid: 15155582
references.citation: Nat Rev Genet. 2012 Feb 07;13(3):163-74
references.pmid: 22310892
references.citation: Genetics. 2001 Aug;158(4):1513-25
references.pmid: 11514443
references.citation: PLoS Genet. 2011 Mar;7(3):e1002010
references.pmid: 21408209
references.citation: Cell. 1990 Dec 21;63(6):1193-204
references.pmid: 2261640
references.citation: Genetics. 1989 Dec;123(4):755-69
references.pmid: 2612895
references.citation: Nucleic Acids Res. 1993 Aug 11;21(16):3691-8
references.pmid: 8367286
references.citation: Science. 2010 Dec 24;330(6012):1775-87
references.pmid: 21177976
references.citation: Development. 2008 Aug;135(14):2373-82
references.pmid: 18550714
references.citation: Genes Dev. 1999 Jun 1;13(11):1453-63
references.pmid: 10364161
references.citation: Genes Dev. 2002 Sep 15;16(18):2390-402
references.pmid: 12231628
references.citation: Development. 2000 Jul;127(14):3119-29
references.pmid: 10862749
references.citation: Curr Biol. 2007 Jun 5;17(11):R425-34
references.pmid: 17550772
references.citation: Nature. 1998 Feb 12;391(6668):691-5
references.pmid: 9490411
references.citation: Genes Dev. 1987 Sep;1(7):731-45
references.pmid: 3428597
references.citation: Nature. 1991 Jan 24;349(6307):346-8
references.pmid: 1702880
references.citation: Nat Rev Genet. 2001 Mar;2(3):175-85
references.pmid: 11256069