GAGA Factor Down-regulates Its Own Promoter

Abstract

GAGA factor is involved in many nuclear transactions, notably in transcription as an activator inDrosophila. The genomic region corresponding to theTrl promoter has been obtained, and a minimal version of a fully active Trl promoter has been defined using transient transfection assays in S2 cells. DNase I footprinting analysis has shown that this region contains multiple GAGA binding sites, suggesting a potential regulatory role of GAGA on its own promoter. The study shows that GAGA down-regulates Trl expression. The repression does not depend on the GAGA isoform, but binding to DNA is absolutely required. A fragment of the Trl promoter can mediate repression to a heterologous promoter only upon GAGA overexpression in transiently transfected S2 cells. Chromatin immunoprecipitation analysis of S2 cells confirmed that GAGA factors are bound to the Trl promoter over a region of 1.4 kbp. Using a double-stranded RNA interference approach, we show that endogenous GAGA factors limit Trl expression in S2 cells. Our results open the possibility of observing similar GAGA repressive effects on other promoters. GAGA factor is involved in many nuclear transactions, notably in transcription as an activator inDrosophila. The genomic region corresponding to theTrl promoter has been obtained, and a minimal version of a fully active Trl promoter has been defined using transient transfection assays in S2 cells. DNase I footprinting analysis has shown that this region contains multiple GAGA binding sites, suggesting a potential regulatory role of GAGA on its own promoter. The study shows that GAGA down-regulates Trl expression. The repression does not depend on the GAGA isoform, but binding to DNA is absolutely required. A fragment of the Trl promoter can mediate repression to a heterologous promoter only upon GAGA overexpression in transiently transfected S2 cells. Chromatin immunoprecipitation analysis of S2 cells confirmed that GAGA factors are bound to the Trl promoter over a region of 1.4 kbp. Using a double-stranded RNA interference approach, we show that endogenous GAGA factors limit Trl expression in S2 cells. Our results open the possibility of observing similar GAGA repressive effects on other promoters. nucleosome remodeling factor Polycomb-responsive element RNase protection assay interference RNA untranslated region cytomegalovirus double stranded GAGA is a Drosophila nuclear factor that is encoded by the Trithorax-like gene (Trl) and is of maternal effect (1Farkas G. Gausz J. Galloni M. Reuter G. Gyurkovics H. Karch F. Nature. 1994; 371: 806-808Crossref PubMed Scopus (342) Google Scholar). At least two isoforms, GAGA519 and GAGA581, are known to be produced by alternative splicing (2Benyajati C. Mueller L., Xu, N. Pappano M. Gao J. Mosammaparast M. Conklin D. Granok H. Craig C. Elgin S. Nucleic Acids Res. 1997; 25: 3345-3353Crossref PubMed Scopus (84) Google Scholar), and both the sequence of the isoforms and their splicing patterns are highly conserved between Drosophila melanogaster and the distant species Drosophila virilis (3Linterman K.-G. Roth G.E. King-Jones K. Korge G. Lehmann M. Dev. Genes Evol. 1998; 208: 447-456Crossref PubMed Scopus (15) Google Scholar). The GAGA factors present an overall modular structure that is formed by an N-terminal BTB/POZ domain involved in protein oligomerization (4Espinás M.L. Jiménez-Garcı́a E. Vaquero A. Canudas S. Bernués J. Azorı́n F. J. Biol. Chem. 1999; 274: 16461-16469Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar, 5Katsani K.R. Hajibagueri Verrijzer C.P. EMBO J. 1999; 18: 698-708Crossref PubMed Scopus (142) Google Scholar); a DNA binding domain, composed of a single zinc-finger and three adjacent basic regions, that confers sequence-specific DNA binding (6Pedone P.V. Ghirlando R. Clore G.M. Gronenborn A.M. Felsenfeld G. Omichinski J.G. Proc. Natl. Acad. Sci. U. S. A. 1995; 93: 2822-2826Crossref Scopus (113) Google Scholar, 7Omichinski J.G. Pedone P.V. Felsenfeld G. Gronenborn A.M. Clore G.M. Nat. Struct. Biol. 1997; 4: 122-132Crossref PubMed Scopus (174) Google Scholar, 8Wilkins R.C. Lis J.T. Nucleic Acids Res. 1998; 26: 2672-2678Crossref PubMed Scopus (65) Google Scholar); and a C-terminal domain (Q-domain) that in both isoforms is glutamine-rich, although the amino acid sequences differ, and is the activation domain (9Vaquero A. Espinás M.L. Azorı́n F. Bernués J. J. Biol. Chem. 2000; 275: 19461-19468Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 10Deleted in proof.Google Scholar, 11Greenberg A.J. Schedl P. Mol. Cell. Biol. 2001; 21: 8565-8574Crossref PubMed Scopus (26) Google Scholar). 1S. Pagans, F. Azorı́n, and J. Bernués, unpublished observations, and A. Vaquero, M. L. Espinás, and J. Bernuês, submitted for publication. There is some evidence that the Q-domain may also be involved in GAGA aggregation (12Agianian B. Leonard K. Bonte E. Van der Zandt H. Becker P.B. Tucker P.A. J. Mol. Biol. 1999; 285: 527-544Crossref PubMed Scopus (27) Google Scholar, 13Wilkins R.C. Lis J.T. J. Mol. Biol. 1999; 285: 515-525Crossref PubMed Scopus (46) Google Scholar). Between the POZ/BTB domain and the DNA-binding domain there is a fourth domain, that will be referred to here as the X-domain, about 200 amino acids long and of unknown structure and properties. To date, both isoforms have been found to be rather equivalent, and have largely overlapping functions in transgenic flies although some differences have been noticed (11Greenberg A.J. Schedl P. Mol. Cell. Biol. 2001; 21: 8565-8574Crossref PubMed Scopus (26) Google Scholar). GAGA binds to DNA sequences with a consensus (GAGAG) (7Omichinski J.G. Pedone P.V. Felsenfeld G. Gronenborn A.M. Clore G.M. Nat. Struct. Biol. 1997; 4: 122-132Crossref PubMed Scopus (174) Google Scholar), but neither a strict consensus nor a single site is efficient enough for GAGA binding. In fact, a GAG or CTC trinucleotide sequence has been described as being sufficient for specific binding (8Wilkins R.C. Lis J.T. Nucleic Acids Res. 1998; 26: 2672-2678Crossref PubMed Scopus (65) Google Scholar). However, as noted by others (14Soeller W.C., Oh, C.E. Kornberg T.B. Mol. Cell. Biol. 1993; PubMed Scopus Google Scholar), GAGA binding on show a to and to GAGA binding is in with the that GAGA is and can with specific sequences that are by other DNA sequences that are neither nor bound (4Espinás M.L. Jiménez-Garcı́a E. Vaquero A. Canudas S. Bernués J. Azorı́n F. J. Biol. Chem. 1999; 274: 16461-16469Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar, 5Katsani K.R. Hajibagueri Verrijzer C.P. EMBO J. 1999; 18: 698-708Crossref PubMed Scopus (142) Google Scholar). The for the of GAGA binding the that GAGA activation is not only single or double are present (4Espinás M.L. Jiménez-Garcı́a E. Vaquero A. Canudas S. Bernués J. Azorı́n F. J. Biol. Chem. 1999; 274: 16461-16469Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar). its GAGA as a transcription activation factor upon binding to transcription of as and R. Cell. Full Text PDF PubMed Scopus Google Scholar, Kornberg Genes Dev. PubMed Scopus Google Scholar). role has been for many other in in R.C. Lis J.T. Nucleic Acids Res. 1997; 25: PubMed Scopus Google Scholar). that GAGA a nuclear GAGA bound to transcription factors are R. B. EMBO J. 1994; PubMed Scopus Google A. S. J. Biol. 1997; Scopus Google Scholar). GAGA is its on the H. Elgin Biol. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar, M.L. Canudas S. L. S. J. Azorı́n F. EMBO 2000; PubMed Scopus Google Scholar, Becker P.B. C. Nature. 1994; PubMed Scopus Google to in the of Drosophila R. B. EMBO J. 1994; PubMed Scopus Google Scholar, A. S. J. Biol. 1997; Scopus Google Scholar). to be to both GAGA isoforms (2Benyajati C. Mueller L., Xu, N. Pappano M. Gao J. Mosammaparast M. Conklin D. Granok H. Craig C. Elgin S. Nucleic Acids Res. 1997; 25: 3345-3353Crossref PubMed Scopus (84) Google Scholar, 11Greenberg A.J. Schedl P. Mol. Cell. Biol. 2001; 21: 8565-8574Crossref PubMed Scopus (26) Google Scholar). the for the on the in in and G. Karch F. Gyurkovics H. Gausz J. Schedl P. PubMed Google Scholar). the evidence that GAGA with remodeling to open Becker P.B. C. Nature. 1994; PubMed Scopus Google Scholar, M. S. Mol. Cell. Biol. 1998; 18: PubMed Scopus Google Scholar). GAGA and the by remodeling present some some on but not on R. L. M. M. G. M. M. C. S. Mol. Cell. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). a has been between GAGA and the The two in and a GAGA region the DNA binding the other the remodeling and the of GAGA have been shown to be in transgenic flies J. Biol. Chem. 2000; 275: Full Text Full Text PDF PubMed Scopus Google Scholar). The of GAGA binding on Polycomb-responsive and its with some of the also a of GAGA with gene H. G. R. EMBO J. 1997; PubMed Scopus Google Scholar, B. C. S. Mol. Cell. Biol. 2000; PubMed Scopus Google Scholar). The of GAGA with a and the of GAGA in a the and the and a with repression M.L. Canudas S. L. S. J. Azorı́n F. EMBO 2000; PubMed Scopus Google Scholar, S. R. Genes Dev. 2001; PubMed Scopus Google Scholar). A for both GAGA and has been to for the of the and the of A. A. F. M. S. 2001; Google Scholar, J. S. A. Karch F. K. Schedl P. Mol. Cell. Biol. 2001; 21: PubMed Scopus Google Scholar). we have the Trl promoter and evidence that both GAGA isoforms can mediate repression of its own promoter. is and GAGA DNA binding and oligomerization are The sequences corresponding to the region to the Trl sequence and in the Drosophila to the sequences corresponding to theTrl promoter. fragment by the using and as and fragment about of promoter the three sequences of the (2Benyajati C. Mueller L., Xu, N. Pappano M. Gao J. Mosammaparast M. Conklin D. Granok H. Craig C. Elgin S. Nucleic Acids Res. 1997; 25: 3345-3353Crossref PubMed Scopus (84) Google Scholar), and the of the GAGA confirmed the genomic sequence on by transfection using in a that sequences a long by or by with specific of between and in The by a fragment of the promoter that the expression of in the to by M. of for GAGA isoforms and in S2 cells using for and have been described (9Vaquero A. Espinás M.L. Azorı́n F. Bernués J. J. Biol. Chem. 2000; 275: 19461-19468Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar). The expression for by the of and the C-terminal region of GAGA519 The expression for by the (4Espinás M.L. Jiménez-Garcı́a E. Vaquero A. Canudas S. Bernués J. Azorı́n F. J. Biol. Chem. 1999; 274: 16461-16469Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar). The the DNA binding domain by the DNA binding domain using that a the in a expression and for expression in S2 cells. the promoter and a gene to and the Trl promoter using an of the for the to or of the for and in an to as as the of the with to the transcription S2 cells and transfected as described (9Vaquero A. Espinás M.L. Azorı́n F. Bernués J. J. Biol. Chem. 2000; 275: 19461-19468Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar). transfection of of to the gene and expression by the promoter of and of The of DNA to by the of of with the to and to for transfection using and for the of three to in The of theTrl promoter to be and sequences between and to the in A. and on GAGA factor in to GAGA519 and and in as described C. 274: PubMed Scopus Google Scholar). DNase I footprinting as described E. Vaquero A. Espinás M.L. R. M. Bernués J. Azorı́n F. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). RNase protection analysis using the the RNA Drosophila S2 and for analysis of Trl of RNA with of on for with and RNA to and to by in transcription using or RNA the sequences in on Drosophila S2 cells and as described H. R. A to in 1997; Scopus Google with the in the described G. R. A Scholar). in GAGA519 using DNA by DNA corresponding to and using the and using a of the results to be in the as by with corresponding of To the fragment of GAGA a protein sequence to both isoforms of GAGA and of the POZ/BTB domain and of the adjacent sequence The by in transcription as described and in To of and for to and transient transfection to to the transfection and the assays as and or as described A for the a fragment about long A DNA fragment by the Drosophila using specific for the Trl The sequence fully with the sequence by in the Drosophila The the of least three transcription to the of the (2Benyajati C. Mueller L., Xu, N. Pappano M. Gao J. Mosammaparast M. Conklin D. Granok H. Craig C. Elgin S. Nucleic Acids Res. 1997; 25: 3345-3353Crossref PubMed Scopus (84) Google Scholar). we to the site the the Our about of the sequence of theTrl gene and of the The study of the Trl promoter transient transfection in S2 a transcription in S2 cells RNase protection assays with RNA S2 cells least three their with to the the and three to the three described (2Benyajati C. Mueller L., Xu, N. Pappano M. Gao J. Mosammaparast M. Conklin D. Granok H. Craig C. Elgin S. Nucleic Acids Res. 1997; 25: 3345-3353Crossref PubMed Scopus (84) Google Scholar). may an in the analysis a of the of the site A and some of the site A is the the the site for of the and the site for the in (2Benyajati C. Mueller L., Xu, N. Pappano M. Gao J. Mosammaparast M. Conklin D. Granok H. Craig C. Elgin S. Nucleic Acids Res. 1997; 25: 3345-3353Crossref PubMed Scopus (84) Google Scholar). In S2 the is we that the site is also the as by the of the The Trl promoter fragment described to a gene and in S2 cells. this with to and as of in analysis A analysis of the Trl promoter that be in to to in a of about of the promoter to only about of and by to of the of the fragment in about of this the is to that the two other and for of that the Trl promoter in S2 cells is and to about analysis of the promoter sequence potential GAGA factor and some potential binding for other regulatory GAGA binds to sequences a of and a binding site has been shown to have rather a single sequence (4Espinás M.L. Jiménez-Garcı́a E. Vaquero A. Canudas S. Bernués J. Azorı́n F. J. Biol. Chem. 1999; 274: 16461-16469Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar, 5Katsani K.R. Hajibagueri Verrijzer C.P. EMBO J. 1999; 18: 698-708Crossref PubMed Scopus (142) Google Scholar, 8Wilkins R.C. Lis J.T. Nucleic Acids Res. 1998; 26: 2672-2678Crossref PubMed Scopus (65) Google Scholar), a DNase I footprinting analysis using GAGA519 factor promoter in S2 cells to we assay to a fragment to and the of the the region to be rather long by as to the of the region that a of GAGA present on theTrl promoter A for a and of in GAGA binding and with and sites, and only and sites, The of the binding not and some a and and and others of and and and results not differences that the of the be in that a DNA upon GAGA binding also noted by an in GAGA factor has been as an activator in the the of its (1Farkas G. Gausz J. Galloni M. Reuter G. Gyurkovics H. Karch F. Nature. 1994; 371: 806-808Crossref PubMed Scopus (342) Google Scholar, 11Greenberg A.J. Schedl P. Mol. Cell. Biol. 2001; 21: 8565-8574Crossref PubMed Scopus (26) Google Scholar, R.C. Lis J.T. Nucleic Acids Res. 1997; 25: PubMed Scopus Google Scholar, G. Karch F. Gyurkovics H. Gausz J. Schedl P. PubMed Google Scholar). GAGA also transcription of many using transient transfection in Drosophila (2Benyajati C. Mueller L., Xu, N. Pappano M. Gao J. Mosammaparast M. Conklin D. Granok H. Craig C. Elgin S. Nucleic Acids Res. 1997; 25: 3345-3353Crossref PubMed Scopus (84) Google Scholar, A. Espinás M.L. Azorı́n F. Bernués J. J. Biol. Chem. 2000; 275: 19461-19468Abstract Full Text Full Text PDF PubMed Scopus (28) Google W.C., Oh, C.E. Kornberg T.B. Mol. Cell. Biol. 1993; PubMed Scopus Google and in transgenic flies J. Biol. Chem. 2000; 275: Full Text Full Text PDF PubMed Scopus Google Scholar). an possibility that GAGA the expression of its own promoter. by transient transfection in GAGA factors and their on the Trl promoter overexpression of GAGA519 or in a repression of the Trl promoter. efficient and a minimal of about with to GAGA of of GAGA factor not in repression not the expression of of GAGA519 transcription of the promoter to in a of an the effect on the of promoter and results not repressive effect of GAGA is on its DNA binding GAGA as in the for their on the long promoter fragment of Trl to Full to the overexpression of RNA interference assays to that the of and the repression of Trl to GAGA repression of Trl as as of by of and specific At the the suggesting a of Trl promoter in the of GAGA and of also not by of and of the not not In to the of GAGA for the repression of the Trl the two GAGA isoforms, GAGA519 and GAGA581, are in sequence for the C-terminal domain (Q-domain) isoforms the as that not for repression the both isoforms transcription of promoter and results not POZ/BTB domain not its not repression However, a single the zinc-finger domain and GAGA to GAGA shown by DNase I footprinting results not repression in GAGA of the Q-domain by the activation domain the and Trl transcription of an factor effect on In analysis by that expression of of the in of the that produced in similar not the DNA binding of GAGA of to the DNA sequence of the Trl promoter that shown in there many GAGA binding on this promoter that of the involved in repression and of that not rather GAGA does not on a but binds of binding (2Benyajati C. Mueller L., Xu, N. Pappano M. Gao J. Mosammaparast M. Conklin D. Granok H. Craig C. Elgin S. Nucleic Acids Res. 1997; 25: 3345-3353Crossref PubMed Scopus (84) Google Scholar, M.L. Jiménez-Garcı́a E. Vaquero A. Canudas S. Bernués J. Azorı́n F. J. Biol. Chem. 1999; 274: 16461-16469Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar, 5Katsani K.R. Hajibagueri Verrijzer C.P. EMBO J. 1999; 18: 698-708Crossref PubMed Scopus (142) Google Scholar, W.C., Oh, C.E. Kornberg T.B. Mol. Cell. Biol. 1993; PubMed Scopus Google Scholar, R. Cell. Full Text PDF PubMed Scopus Google Scholar, R.C. Lis J.T. Nucleic Acids Res. 1997; 25: PubMed Scopus Google Scholar). we to rather that The region for GAGA to Trl using the promoter described to in S2 cells effect on repression to the repression not be of the results that the promoter element involved in repression to be between and To and assay region we that repression be to heterologous promoters. To an a that the promoter to be to GAGA found to be and to to the to of the and and in an to as as the of the Trl promoter with to the transcription site of the promoter. of in S2 cells in transcription of the gene for the suggesting that some sequence The to not show of not for of the Trl promoter and mediate repression of the promoter with to their corresponding and about of the with the Trl promoter only The repression with fragment not the other GAGA overexpression effect on and transcription and results that a region of the Trl promoter repression to an heterologous promoter and the Trl defined and in the promoter for that the repression be to of a repressive element of the of a fragment the and of the promoter in of repression only upon GAGA overexpression of In the of GAGA of this region in a of transcription as for the To some the of the genomic Trl promoter in we immunoprecipitation Using as the described for the footprinting to the of GAGA the minimal region GAGA be bound to of although a of GAGA factors on and of GAGA factors region of the to mediate repression to a heterologous promoter. in binding of GAGA shown to have in the assay highly in GAGA factors as of GAGA similar but for the other three and and for the the results by DNase I and that GAGA have a regulatory role on its own promoter. the repressive effect on theTrl promoter also be in S2 cells by of the endogenous GAGA using RNA interference of the Trl and of GAGA in a of transcription that an the in this GAGA not but the endogenous of GAGA we that of GAGA factors limit Trl transcription in S2 cells that a in the GAGA results in a promoter. A promoter of the Trl gene has been and the for expression in S2 cells A region of about of the transcription site sufficient to transcription in S2 cells. to a only and only results in transgenic flies results and that both the to promoter and the minimal to promoter to be and to similar expression of a the to not transcription of the Trl gene have been in S2 cells that with the of the three a Drosophila (2Benyajati C. Mueller L., Xu, N. Pappano M. Gao J. Mosammaparast M. Conklin D. Granok H. Craig C. Elgin S. Nucleic Acids Res. 1997; 25: 3345-3353Crossref PubMed Scopus (84) Google Scholar). In the of other two has been the site in with of the by for The of other be this to the in of the Trl promoter sequence potential GAGA factor binding that confirmed by DNase I footprinting In fact, as many as in an region the transcription sites, and there may be some others that not be in not to an of the GAGA binding on this and in fact, this of not The analysis of the that of GAGA sequences of (7Omichinski J.G. Pedone P.V. Felsenfeld G. Gronenborn A.M. Clore G.M. Nat. Struct. Biol. 1997; 4: 122-132Crossref PubMed Scopus (174) Google Scholar). the sites, least a trinucleotide sequence that in to GAGA factor (8Wilkins R.C. Lis J.T. Nucleic Acids Res. 1998; 26: 2672-2678Crossref PubMed Scopus (65) Google Scholar), and not present sequence of a GAGA of the be with the the some others of the in results on the and to the of GAGA some may of and be by sites, and some binding may a GAGA binding not be as has been (4Espinás M.L. Jiménez-Garcı́a E. Vaquero A. Canudas S. Bernués J. Azorı́n F. J. Biol. Chem. 1999; 274: 16461-16469Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar, GAGA factor activator of Scholar). Our results are in with a of GAGA to (14Soeller W.C., Oh, C.E. Kornberg T.B. Mol. Cell. Biol. 1993; PubMed Scopus Google Scholar). of the to be as two GAGA binding sites, and in the to be on suggesting that both sequences are results an GAGA binding have been for other K.R. Hajibagueri Verrijzer C.P. EMBO J. 1999; 18: 698-708Crossref PubMed Scopus (142) Google Scholar, R. Cell. Full Text PDF PubMed Scopus Google Scholar, Mol. Cell. Biol. 1997; PubMed Scopus Google Scholar). results a potential of by GAGA GAGA factors have been to transcription of promoter but to transcription we have shown for the promoter. The of GAGA binding on the promoter shown and to be GAGA K.R. Hajibagueri Verrijzer C.P. EMBO J. 1999; 18: 698-708Crossref PubMed Scopus (142) Google Scholar, D. Mol. Cell. Biol. PubMed Scopus Google Scholar). of GAGA519 or to a of Trl that transcription to The results that neither the Q-domain nor POZ/BTB domain for a single amino acid the zinc-finger DNA binding domain largely in the of the POZ/BTB domain GAGA binds as a and structure on the promoter (4Espinás M.L. Jiménez-Garcı́a E. Vaquero A. Canudas S. Bernués J. Azorı́n F. J. Biol. Chem. 1999; 274: 16461-16469Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar, 5Katsani K.R. Hajibagueri Verrijzer C.P. EMBO J. 1999; 18: 698-708Crossref PubMed Scopus (142) Google Scholar), GAGA repressive the other the that this repression can be to a activation by the activation domain may be that to other factors may not be the only GAGA is to Trl transcription of some promoter is a of the Q-domain activation to repression the Q-domain is the other the with be by the promoter that Mol. Cell. Biol. 1995; PubMed Scopus Google a similar activation for this using a promoter that to activation by not the of its activation potential is to be the of the (9Vaquero A. Espinás M.L. Azorı́n F. Bernués J. J. Biol. Chem. 2000; 275: 19461-19468Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar). Our results that the GAGA DNA binding domain on its own or in with the may be for the repression of the Trl promoter. In a double has shown that the POZ/BTB domain and not as repressive that be sufficient for repression in with the DNA binding domain not The of the Trl gene by its GAGA519 and that of GAGA is a in S2 cells. In fact, endogenous GAGA gene is a of repression is not S2 cells of GAGA a of GAGA can be on the Trl on the region that has been shown to mediate The of a GAGA be to in GAGA be a to the the of GAGA factor and its binding to this In is that GAGA is but rather in with other be that are not and the of least an factor can be In the upon with some GAGA the repressive Using in GAGA binding a or in minimal in this is GAGA only transcription in and in (2Benyajati C. Mueller L., Xu, N. Pappano M. Gao J. Mosammaparast M. Conklin D. Granok H. Craig C. Elgin S. Nucleic Acids Res. 1997; 25: 3345-3353Crossref PubMed Scopus (84) Google Scholar, M.L. Jiménez-Garcı́a E. Vaquero A. Canudas S. Bernués J. Azorı́n F. J. Biol. Chem. 1999; 274: 16461-16469Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar, A. Espinás M.L. Azorı́n F. Bernués J. J. Biol. Chem. 2000; 275: 19461-19468Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, W.C., Oh, C.E. Kornberg T.B. Mol. Cell. Biol. 1993; PubMed Scopus Google Scholar, J. Biol. Chem. 2000; 275: Full Text Full Text PDF PubMed Scopus Google Scholar, E. Vaquero A. Espinás M.L. R. M. Bernués J. Azorı́n F. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). results GAGA be as a the other the factor that repression of the Trl promoter be specific for this promoter and GAGA binding to the of a DNA binding site for the unknown in the of the GAGA the can be to the promoter by the is not with other The that of promoter can mediate GAGA on its the of binding or for the unknown factor in region or the of two or and to or the other In this GAGA to both and as a factor to In with this other the Trl in some GAGA binding sites, not suggesting that although GAGA factors GAGA519 or are are not has a in although is an its binding to a region of the gene results in of the does not with but the of an DNA element by binding and with in the of and results in its to a G. A.J. Genes Dev. 1997; PubMed Scopus Google Scholar, G. J. S. R. A.J. Mol. Cell. Biol. 1998; 18: PubMed Scopus Google Scholar). The that GAGA an factor the Trl in a that transcription is not but The also in this an activator to bound enough to some GAGA in the region that can be by of To GAGA binding does not in some we have to that the unknown activator is largely active GAGA promoter is not to has a in transcription the promoter of the the in its binding to the promoter with a of the factor this to a repression of its own transcription R. Cell. Full Text PDF PubMed Scopus Google Scholar, R. EMBO J. PubMed Scopus Google Scholar). The of a GAGA site on a promoter be to an activation of GAGA binding to a promoter results in activation or be encoded in the specific DNA sequence of the promoter and depend on other in the that GAGA factors are this is not