title: Enhancer-promoter communication at the Drosophila engrailed locus.
abstract: Enhancers are often located many tens of kilobases away from the promoter they regulate, sometimes residing closer to the promoter of a neighboring gene. How do they know which gene to activate? We have used homing P[en] constructs to study the enhancer-promoter communication at the engrailed locus. Here we show that engrailed enhancers can act over large distances, even skipping over other transcription units, choosing the engrailed promoter over those of neighboring genes. This specificity is achieved in at least three ways. First, early acting engrailed stripe enhancers exhibit promoter specificity. Second, a proximal promoter-tethering element is required for the action of the imaginal disc enhancer(s). Our data suggest that there are two partially redundant promoter-tethering elements. Third, the long-distance action of engrailed enhancers requires a combination of the engrailed promoter and sequences within or closely linked to the promoter proximal Polycomb-group response elements. These data show that multiple mechanisms ensure proper enhancer-promoter communication at the Drosophila engrailed locus.
authors.affiliation: Laboratory of Molecular Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Kwon
authors.forename: Diane
authors.initials: D
authors.lastname: Mucci
authors.forename: Kristofor K
authors.initials: KK
authors.lastname: Langlais
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Americo
authors.forename: Sarah K
authors.initials: SK
authors.lastname: DeVido
authors.forename: Yuzhong
authors.initials: Y
authors.lastname: Cheng
authors.forename: Judith A
authors.initials: JA
authors.lastname: Kassis
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D007301:Insect Hormones / Q000235:genetics; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C063459:En protein, Drosophila; D018398:Homeodomain Proteins; D007301:Insect Hormones; D014157:Transcription Factors; C087983:inv protein, Drosophila
references.citation: Genes Dev. 2002 Oct 15;16(20):2583-92
references.pmid: 12381658
references.citation: Genes Dev. 1988 Jan;2(1):68-81
references.pmid: 3356339
references.citation: Genes Dev. 1996 Mar 15;10(6):711-24
references.pmid: 8598298
references.citation: Development. 1999 May;126(9):1793-803
references.pmid: 10101114
references.citation: Development. 1997 Apr;124(8):1531-41
references.pmid: 9108369
references.citation: Curr Opin Cell Biol. 2008 Jun;20(3):253-9
references.pmid: 18436437
references.citation: Genes Cells. 1999 Apr;4(4):205-18
references.pmid: 10336692
references.citation: Mol Cell Biol. 1997 Dec;17(12):6773-83
references.pmid: 9372908
references.citation: Genes Dev. 2001 Oct 1;15(19):2515-9
references.pmid: 11581157
references.citation: PLoS Biol. 2006 Jun;4(6):e170
references.pmid: 16613483
references.citation: Mol Cell Biol. 2000 Jul;20(13):4754-64
references.pmid: 10848601
references.citation: Nature. 1988 Apr 14;332(6165):604-9
references.pmid: 3282172
references.citation: Genetics. 1991 Aug;128(4):751-61
references.pmid: 1655566
references.citation: J Exp Biol. 2004 Jun;207(Pt 13):2323-38
references.pmid: 15159437
references.citation: Genes Dev. 2008 Oct 15;22(20):2823-30
references.pmid: 18923080
references.citation: Development. 1998 Oct;125(20):4055-66
references.pmid: 9735366
references.citation: Cell. 1985 Nov;43(1):59-69
references.pmid: 3935318
references.citation: Nat Genet. 2006 Jun;38(6):700-5
references.pmid: 16732288
references.citation: Genome Biol. 2002;3(12):RESEARCH0088
references.pmid: 12537577
references.citation: Development. 2007 Jan;134(2):223-32
references.pmid: 17185323
references.citation: Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9243-7
references.pmid: 12093913
references.citation: Nat Genet. 1997 Jun;16(2):171-3
references.pmid: 9171828
references.citation: Genes Dev. 1998 Feb 15;12(4):547-56
references.pmid: 9472023
references.citation: Genes Dev. 1990 Mar;4(3):433-43
references.pmid: 2110923
references.citation: Development. 2009 Sep;136(18):3077-87
references.pmid: 19675129
references.citation: Development. 2008 Jan;135(1):123-31
references.pmid: 18045839
references.citation: Nat Rev Genet. 2006 Sep;7(9):703-13
references.pmid: 16909129
references.citation: Genetics. 1992 May;131(1):79-90
references.pmid: 1375573
references.citation: Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12696-700
references.pmid: 7809104
references.citation: Genes Dev. 1989 Sep;3(9):1273-87
references.pmid: 2558049
references.citation: Genes Dev. 1996 May 15;10(10):1260-70
references.pmid: 8675012
references.citation: Genes Dev. 1990 Jul;4(7):1079-93
references.pmid: 1976568
references.citation: Genes Dev. 2001 Oct 1;15(19):2503-8
references.pmid: 11581155
references.citation: Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6856-61
references.pmid: 10359803
references.citation: Development. 2008 Feb;135(4):669-76
references.pmid: 18199580
references.citation: Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1919-23
references.pmid: 1311855
references.citation: Genes Dev. 1987 Mar;1(1):19-28
references.pmid: 2892756
references.citation: Curr Opin Genet Dev. 2006 Oct;16(5):476-84
references.pmid: 16914306
references.citation: Science. 2008 Sep 5;321(5894):1314
references.pmid: 18772429
references.citation: Genetics. 1996 Mar;142(3):893-906
references.pmid: 8849895
references.citation: Dev Cell. 2008 Dec;15(6):877-89
references.pmid: 18993116
references.citation: Genetics. 1994 Mar;136(3):1025-38
references.pmid: 8005412
references.citation: Development. 2000 Sep;127(18):3981-92
references.pmid: 10952896
references.citation: Cell. 1985 Aug;42(1):309-16
references.pmid: 2990728