title: The POU transcription factor Drifter/Ventral veinless regulates expression of Drosophila immune defense genes.
abstract: Innate immunity operates as a first line of defense in multicellular organisms against infections caused by different classes of microorganisms. Antimicrobial peptides (AMPs) are synthesized constitutively in barrier epithelia to protect against microbial attack and are also upregulated in response to infection. Here, we implicate Drifter/Ventral veinless (Dfr/Vvl), a class III POU domain transcription factor, in tissue-specific regulation of the innate immune defense of Drosophila. We show that Dfr/Vvl is highly expressed in a range of immunocompetent tissues, including the male ejaculatory duct, where its presence overlaps with and drives the expression of cecropin, a potent broad-spectrum AMP. Dfr/Vvl overexpression activates transcription of several AMP genes in uninfected flies in a Toll pathway- and Imd pathway-independent manner. Dfr/Vvl activates a CecA1 reporter gene both in vitro and in vivo by binding to an upstream enhancer specific for the male ejaculatory duct. Further, Dfr/Vvl and the homeodomain protein Caudal (Cad) activate transcription synergistically via this enhancer. We propose that the POU protein Dfr/Vvl acts together with other regulators in a combinatorial manner to control constitutive AMP gene expression in a gene-, tissue-, and sex-specific manner, thus promoting a first-line defense against infection in tissues that are readily exposed to pathogens.
authors.affiliation: Department of Molecular Biology and Functional Genomics, Stockholm University, SE-106 91 Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Junell
authors.forename: Hanna
authors.initials: H
authors.lastname: Uvell
authors.forename: Monica M
authors.initials: MM
authors.lastname: Davis
authors.forename: Esther
authors.initials: E
authors.lastname: Edlundh-Rose
authors.forename: Asa
authors.initials: A
authors.lastname: Antonsson
authors.forename: Leslie
authors.initials: L
authors.lastname: Pick
authors.forename: Ylva
authors.initials: Y
authors.lastname: Engström
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004330:Drosophila / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005260:Female; D017344:Genes, Insect; D005837:Genitalia, Male / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate / Q000235:genetics*; D008297:Male; D008954:Models, Biological; D009154:Mutation; D050809:POU Domain Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D023181:Antimicrobial Cationic Peptides; D017931:DNA Primers; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D050809:POU Domain Factors; D012333:RNA, Messenger; D014157:Transcription Factors; C084564:cad protein, Drosophila; C091575:vvl protein, Drosophila; C031161:cecropin A
references.citation: Mech Dev. 2000 Mar 1;91(1-2):163-73
references.pmid: 10704841
references.citation: Nat Rev Microbiol. 2007 Apr;5(4):264-77
references.pmid: 17363965
references.citation: Curr Top Microbiol Immunol. 2006;306:67-90
references.pmid: 16909918
references.citation: Development. 2003 Jun;130(11):2467-78
references.pmid: 12702660
references.citation: Trends Genet. 2007 Jul;23(7):342-9
references.pmid: 17532525
references.citation: Physiol Genomics. 2005 Sep 21;23(1):5-17
references.pmid: 16033865
references.citation: Trends Genet. 1991 Apr;7(4):119-25
references.pmid: 2068782
references.citation: EMBO Rep. 2000 Oct;1(4):347-52
references.pmid: 11269501
references.citation: EMBO J. 1999 Jul 15;18(14):4013-22
references.pmid: 10406806
references.citation: Immunol Rev. 2004 Apr;198:169-84
references.pmid: 15199962
references.citation: Development. 1995 Oct;121(10):3405-16
references.pmid: 7588073
references.citation: Curr Biol. 2004 Aug 24;14(16):1509-14
references.pmid: 15324670
references.citation: Development. 2000 Jul;127(14):3173-83
references.pmid: 10862753
references.citation: Mol Cell Biol. 1996 Apr;16(4):1813-23
references.pmid: 8657157
references.citation: Development. 1997 Sep;124(17):3273-81
references.pmid: 9310322
references.citation: Curr Biol. 2005 Sep 20;15(18):1690-4
references.pmid: 16169493
references.citation: J Immunol. 2004 Nov 1;173(9):5398-405
references.pmid: 15494486
references.citation: Mamm Genome. 2006 Apr;17(4):332-9
references.pmid: 16596454
references.citation: Nat Rev Immunol. 2007 Mar;7(3):179-90
references.pmid: 17318230
references.citation: Annu Rev Immunol. 2007;25:697-743
references.pmid: 17201680
references.citation: Genes Dev. 1995 Jan 1;9(1):123-37
references.pmid: 7828848
references.citation: Curr Opin Immunol. 2003 Feb;15(1):12-9
references.pmid: 12495727
references.citation: Nature. 2003 Apr 3;422(6931):522-6
references.pmid: 12660734
references.citation: Nature. 1990 Feb 1;343(6257):467-70
references.pmid: 1967821
references.citation: Dev Genet. 1996;18(4):279-88
references.pmid: 8754279
references.citation: J Mol Biol. 1993 Jul 20;232(2):327-33
references.pmid: 8345514
references.citation: Endocrinology. 2006 Apr;147(4):1950-8
references.pmid: 16373422
references.citation: Nucleic Acids Res. 1997 Mar 15;25(6):1233-9
references.pmid: 9092634
references.citation: Infect Disord Drug Targets. 2008 Sep;8(3):144-55
references.pmid: 18782031
references.citation: Nat Rev Genet. 2001 Apr;2(4):256-67
references.pmid: 11283698
references.citation: Immunity. 2000 Nov;13(5):737-48
references.pmid: 11114385
references.citation: Development. 2004 Nov;131(21):5429-39
references.pmid: 15469973
references.citation: EMBO J. 1991 Jan;10(1):163-9
references.pmid: 1899226
references.citation: Mol Immunol. 2004 Nov;41(11):1099-108
references.pmid: 15476921
references.citation: Infect Immun. 2000 Jul;68(7):4297-302
references.pmid: 10858248
references.citation: Dev Comp Immunol. 1999 Jun-Jul;23(4-5):345-58
references.pmid: 10426427
references.citation: Mech Dev. 2000 Mar 1;91(1-2):271-8
references.pmid: 10704851
references.citation: Methods. 2001 Dec;25(4):383-5
references.pmid: 11846607
references.citation: Genes Dev. 1989 May;3(5):676-86
references.pmid: 2501149
references.citation: Immunol Rev. 2004 Apr;198:83-96
references.pmid: 15199956
references.citation: Science. 1999 Oct 1;286(5437):113-7
references.pmid: 10506557
references.citation: Biopolymers. 2002;66(4):236-48
references.pmid: 12491537
references.citation: Mol Immunol. 2003 Nov;40(7):413-21
references.pmid: 14568387
references.citation: Mol Cell Biol. 2008 Aug;28(15):4883-95
references.pmid: 18519585
references.citation: Reprod Biol Endocrinol. 2006 Feb 04;4:7
references.pmid: 16457734
references.citation: Science. 2008 Feb 8;319(5864):777-82
references.pmid: 18218863
references.citation: Science. 2002 Nov 1;298(5595):1025-9
references.pmid: 12411706
references.citation: J Am Soc Nephrol. 2006 Dec;17(12):3267-3272
references.pmid: 37001006
references.citation: Nat Immunol. 2005 Jun;6(6):551-7
references.pmid: 15908936
references.citation: Cell. 2006 Feb 24;124(4):783-801
references.pmid: 16497588
references.citation: Nature. 1986 Jan 9-15;319(6049):154-8
references.pmid: 3079885
references.citation: Mol Cell Biol. 2003 Nov;23(22):8272-81
references.pmid: 14585984
references.citation: Fly (Austin). 2008 Jul-Aug;2(4):215-9
references.pmid: 18769140
references.citation: Development. 2001 Mar;128(5):779-90
references.pmid: 11171402
references.citation: Endocr Rev. 2001 Feb;22(1):2-35
references.pmid: 11159814
references.citation: Mol Cell Biol. 2004 Jan;24(1):172-85
references.pmid: 14673153
references.citation: Development. 1993 Jun;118(2):401-15
references.pmid: 8223268
references.citation: Insect Biochem Mol Biol. 2007 Mar;37(3):202-12
references.pmid: 17296495
references.citation: Genetics. 2007 Feb;175(2):777-83
references.pmid: 17110486
references.citation: EMBO J. 1998 Aug 10;17(5):1217-27
references.pmid: 9482719
references.citation: Genes Dev. 1988 Dec;2(12A):1513-6
references.pmid: 3215510
references.citation: Insect Mol Biol. 1998 Feb;7(1):51-62
references.pmid: 9459429
references.citation: Biochim Biophys Acta. 2006 Sep;1758(9):1408-25
references.pmid: 16716248
references.citation: J Neurosci. 2000 Jun 15;20(12):4596-605
references.pmid: 10844029
references.citation: Genes Dev. 1997 May 15;11(10):1207-25
references.pmid: 9171367
references.citation: Nature. 1988 Dec 8;336(6199):601-4
references.pmid: 2904656
references.citation: Science. 2006 Mar 24;311(5768):1770-3
references.pmid: 16497887
references.citation: Cell. 1987 Feb 13;48(3):465-78
references.pmid: 2433048
references.citation: Nature. 2002 Jan 24;415(6870):389-95
references.pmid: 11807545
references.citation: Nature. 2001 Nov 22;414(6862):454-7
references.pmid: 11719807
references.citation: Development. 1996 Dec;122(12):4169-78
references.pmid: 9012536
references.citation: Cell. 1993 Nov 19;75(4):753-63
references.pmid: 8242747
references.citation: PLoS Pathog. 2009 Dec;5(12):e1000694
references.pmid: 20019799
references.citation: Methods Cell Biol. 1994;44:445-87
references.pmid: 7707967
references.citation: Mech Dev. 2006 Jan;123(1):76-83
references.pmid: 16326080
references.citation: J Immunol. 2006 Feb 15;176(4):2455-64
references.pmid: 16456005
references.citation: Cell Mol Life Sci. 2008 Jul;65(13):2069-79
references.pmid: 18360739
references.citation: EMBO J. 1990 Sep;9(9):2969-76
references.pmid: 2390977
references.citation: Nature. 2007 Nov 8;450(7167):219-32
references.pmid: 17994088