Identification of transcriptional targets of the dual-function transcription factor/phosphatase eyes absent.
Drosophila eye specification and development relies on a collection of transcription factors termed the retinal determination gene network (RDGN). Two members of this network, Eyes absent (EYA) and Sine oculis (SO), form a transcriptional complex in which EYA provides the transactivation function while SO provides the DNA binding activity. EYA also functions as a protein tyrosine phosphatase, raising the question of whether transcriptional output is dependent or independent of phosphatase activity. To explore this, we used microarrays together with binding site analysis, quantitative real-time PCR, chromatin immunoprecipitation, genetics and in vivo expression analysis to identify new EYA-SO targets. In parallel, we examined the expression profiles of tissue expressing phosphatase mutant eya and found that reducing phosphatase activity did not globally impair transcriptional output. Among the targets identified by our analysis was the cell cycle regulatory gene, string (stg), suggesting that EYA and SO may influence cell proliferation through transcriptional regulation of stg. Future investigation into the regulation of stg and other EYA-SO targets identified in this study will help elucidate the transcriptional circuitries whereby output from the RDGN integrates with other signaling inputs to coordinate retinal development.
Jemc
Jennifer
J
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Rebay
Ilaria
I
D000818:Animals; D018797:Cell Cycle Proteins; D054910:Compound Eye, Arthropod / Q000254:growth & development / Q000378:metabolism*; D004330:Drosophila / Q000254:growth & development / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; C087345:So protein, Drosophila; D014157:Transcription Factors; C092694:eya protein, Drosophila; D017027:Protein Tyrosine Phosphatases; C059217:stg protein, Drosophila
Development. 2005 Jun;132(12):2771-82
15901665
Genetics. 2005 Jun;170(2):687-95
15802522
Dev Biol. 2005 Oct 1;286(1):158-68
16125693
Development. 2005 Nov;132(21):4833-43
16207753
Mol Cell Biol. 2005 Dec;25(24):10711-20
16314497
Cancer Res. 2006 Feb 15;66(4):1982-9
16488997
Genome Res. 2006 Apr;16(4):466-76
16533912
Dev Biol. 2006 Jun 1;294(1):220-31
16595131
Dev Biol. 2006 Sep 15;297(2):536-49
16780828
Development. 2006 Dec;133(24):4881-9
17108002
Dev Biol. 2007 Mar 15;303(2):756-71
17137572
Dev Biol. 2000 May 15;221(2):355-64
10790331
Genetics. 2000 Jun;155(2):709-20
10835393
Mol Microbiol. 2000 Oct;38(1):114-25
11029694
Bioinformatics. 2000 Dec;16(12):1145-50
11159333
Biochem Biophys Res Commun. 2001 Apr 20;282(5):1194-200
11302742
Mol Cell Biol. 2001 May;21(10):3343-50
11313460
Dev Cell. 2001 Jul;1(1):51-61
11703923
Development. 2001 Dec;128(23):4737-46
11731454
Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):763-8
11752406
Development. 2002 Feb;129(3):625-34
11830564
Structure. 2002 Jun;10(6):787-95
12057194
Dev Genes Evol. 2002 Jul;212(6):267-76
12111211
Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9888-93
12107285
Nat Cell Biol. 2002 Dec;4(12):976-80
12447387
Development. 2003 May;130(10):2239-52
12668636
Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4024-9
12655063
Dev Biol. 2003 Jun 1;258(1):117-28
12781687
Development. 2003 Jul;130(14):3085-94
12783782
Mol Cell Biol. 2003 Sep;23(17):5989-99
12917324
Dev Biol. 2003 Nov 15;263(2):323-9
14597205
Nature. 2003 Nov 20;426(6964):247-54
14628042
Nature. 2003 Nov 20;426(6964):295-8
14628052
Nature. 2003 Nov 20;426(6964):299-302
14628053
Nat Med. 2004 Feb;10(2):175-81
14704789
Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6478-83
15123840
Mol Cell Biol. 1990 Feb;10(2):634-42
2105456
Science. 1991 Nov 29;254(5036):1385-7
1683715
Cell. 1992 Jun 12;69(6):977-88
1606618
Cell. 1993 Feb 12;72(3):379-95
8431945
Neuron. 1994 May;12(5):977-96
7910468
Science. 1994 Aug 5;265(5173):785-9
7914031
Cell Growth Differ. 1994 Jun;5(6):585-93
8086336
Development. 1994 Dec;120(12):3473-86
7821215
Science. 1995 Mar 24;267(5205):1788-92
7892602
Cell. 1996 Feb 9;84(3):421-30
8608596
Development. 1997 Jan;124(1):45-52
9006066
Nat Genet. 1997 Feb;15(2):157-64
9020840
Genome Res. 1997 Feb;7(2):128-41
9049631
Development. 1997 Mar;124(5):971-82
9056773
Cell. 1997 Mar 21;88(6):789-99
9118222
Biochemistry. 1997 Mar 25;36(12):3680-6
9132021
Nature. 1997 Jul 17;388(6639):304-8
9230443
Proc Natl Acad Sci U S A. 1997 Oct 28;94(22):11974-9
9342347
Cell. 1997 Dec 26;91(7):881-91
9428512
Cell. 1997 Dec 26;91(7):893-903
9428513
Dev Biol. 1998 Apr 1;196(1):42-57
9527880
Int J Biochem Cell Biol. 1997 Dec;29(12):1371-87
9570133
Development. 1998 Jun;125(12):2181-91
9584118
Cell. 1998 Jun 26;93(7):1183-93
9657151
Nature. 1998 Jul 2;394(6688):82-4
9665132
Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12608-13
9770533
J Biol Chem. 1998 Nov 20;273(47):31297-307
9813038
Development. 1999 May;126(9):1793-803
10101114
Mol Cell. 1999 Mar;3(3):297-307
10198632
Genes Dev. 1999 Dec 15;13(24):3231-43
10617572
Genetics. 2000 Jan;154(1):237-46
10628984
Hum Mol Genet. 2000 Feb 12;9(3):363-6
10655545
Development. 1997 Dec;124(23):4819-26
9428418
Development. 1999 May;126(10):2253-60
10207149
Nat Genet. 1999 Sep;23(1):113-7
10471511
Mol Cell Biol. 1999 Oct;19(10):6815-24
10490620
Cancer Res. 2005 Feb 1;65(3):925-32
15705892
Nat Genet. 2005 Mar;37(3):221-3
15696165
Development. 2005 May;132(9):2235-49
15788460