title: The Drosophila over compensating males gene genetically inhibits dosage compensation in males.
abstract: Male Drosophila are monosomic for the X chromosome, but survive due to dosage compensation. They use the Male Specific Lethal (MSL) complex composed of noncoding roX RNA and histone modifying enzymes to hypertranscribe most genes along the X ∼1.6-1.8 fold relative to each female allele. It is not known how the MSL complex achieves this precise adjustment to a large and diverse set of target genes. We carried out a genetic screen searching for novel factors that regulate dosage compensation in flies. This strategy generated thirty alleles in a previously uncharacterized gene, over compensating males (ocm) that antagonizes some aspect of MSL activity. The mutations were initially recovered because they derepressed an MSL-dependent eye color reporter. Null ocm mutations are lethal to both sexes early in development revealing an essential function. Combinations of hypomorphic ocm alleles display a male specific lethality similar to mutations in the classic msl genes, but ocm males die due to excessive, rather than lack of dosage compensation. Males that die due to very low MSL activity can be partially rescued by ocm mutations. Likewise, males that would die from ocm mutations can be rescued by reducing the dose of various msl and roX genes. ocm encodes a large nuclear protein that shares a novel cysteine rich motif with known transcription factors.
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, TX, USA. leonlimck@bics.bwh.harvard.edu
authors.forename: Chiat Koo
authors.initials: CK
authors.lastname: Lim
authors.forename: Richard L
authors.initials: RL
authors.lastname: Kelley
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004303:Dosage Compensation, Genetic / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014960:X Chromosome / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C082132:msl-1 protein, Drosophila; C094166:msl-2 protein, Drosophila; C454144:roX1 protein, Drosophila; C093904:msl-3 protein, Drosophila
references.citation: Nature. 1997 May 8;387(6629):195-9
references.pmid: 9144292
references.citation: Genes Dev. 2005 Oct 1;19(19):2284-8
references.pmid: 16204179
references.citation: Nature. 2011 Mar 3;471(7336):115-8
references.pmid: 21368835
references.citation: EMBO J. 1999 Dec 15;18(24):7019-28
references.pmid: 10601024
references.citation: Mol Cell. 2012 Nov 30;48(4):647-54
references.pmid: 23084834
references.citation: Annu Rev Genet. 1996;30:637-702
references.pmid: 8982468
references.citation: Mol Cell Biol. 2005 Aug;25(15):6798-810
references.pmid: 16024812
references.citation: Cell. 1995 Jun 16;81(6):867-77
references.pmid: 7781064
references.citation: BMC Biol. 2010 Jun 10;8:80
references.pmid: 20537125
references.citation: Proc Natl Acad Sci U S A. 1990 Dec;87(24):9923-7
references.pmid: 2124708
references.citation: Mol Cell Biol. 2005 Jul;25(14):5947-54
references.pmid: 15988010
references.citation: PLoS Genet. 2012;8(7):e1002830
references.pmid: 22844249
references.citation: J Genet Genomics. 2011 Aug 20;38(8):327-32
references.pmid: 21867958
references.citation: Genetics. 2003 Oct;165(2):601-12
references.pmid: 14573473
references.citation: J Biol Chem. 2001 Aug 24;276(34):31483-6
references.pmid: 11445559
references.citation: Genes Dev. 2005 Oct 1;19(19):2289-94
references.pmid: 16204180
references.citation: EMBO J. 2002 Mar 1;21(5):1084-91
references.pmid: 11867536
references.citation: Genes Dev. 2003 Jun 1;17(11):1334-9
references.pmid: 12782651
references.citation: Science. 2010 Dec 24;330(6012):1787-97
references.pmid: 21177974
references.citation: Science. 2002 Nov 22;298(5598):1620-3
references.pmid: 12446910
references.citation: Nat Struct Mol Biol. 2008 Dec;15(12):1318-25
references.pmid: 19029895
references.citation: Cell. 2011 Oct 28;147(3):690-703
references.pmid: 22036573
references.citation: Nat Rev Genet. 2012 Jan 18;13(2):123-34
references.pmid: 22251873
references.citation: EMBO J. 2000 Jan 4;19(1):144-55
references.pmid: 10619853
references.citation: Science. 2012 Aug 10;337(6095):742-6
references.pmid: 22821985
references.citation: Mol Cell. 2007 Oct 12;28(1):121-33
references.pmid: 17936709
references.citation: EMBO J. 2004 Jun 2;23(11):2258-68
references.pmid: 15141166
references.citation: Mol Cell Biol. 2005 Nov;25(21):9175-88
references.pmid: 16227571
references.citation: Methods Cell Biol. 1994;44:655-81
references.pmid: 7707974
references.citation: Science. 1982 Oct 22;218(4570):348-53
references.pmid: 6289436
references.citation: Mech Dev. 2008 Nov-Dec;125(11-12):1009-19
references.pmid: 18793722
references.citation: Dev Cell. 2012 Mar 13;22(3):610-24
references.pmid: 22421046
references.citation: Nucleic Acids Res. 2010 Jun;38(10):3209-21
references.pmid: 20139418
references.citation: Mol Cell. 2000 Feb;5(2):367-75
references.pmid: 10882077
references.citation: Nat Methods. 2009 Jun;6(6):431-4
references.pmid: 19465919
references.citation: J Mol Evol. 2003 May;56(5):527-39
references.pmid: 12698291
references.citation: Nat Struct Mol Biol. 2010 Aug;17(8):1027-9
references.pmid: 20657587
references.citation: Genetics. 2003 Jun;164(2):565-74
references.pmid: 12807777
references.citation: Mol Cell. 2011 Jul 8;43(1):132-44
references.pmid: 21726816
references.citation: PLoS Genet. 2012;8(6):e1002736
references.pmid: 22723752
references.citation: Curr Biol. 2000 Feb 10;10(3):136-43
references.pmid: 10679323
references.citation: Genetics. 2006 Dec;174(4):1859-66
references.pmid: 17028315
references.citation: Mol Cell. 2006 Mar 17;21(6):811-23
references.pmid: 16543150
references.citation: Mol Cell Biol. 2008 Feb;28(3):958-66
references.pmid: 18039854
references.citation: PLoS Genet. 2012;8(3):e1002564
references.pmid: 22438819