Specific expression of the glucagon gene in the rat pancreas requires the presence of the G1 element localized at -100/-49 base pairs on the promoter. Although it is known that multiple transcription factors such as Pax-6, Cdx-2/3, c-Maf, Maf-B, and Brain-4 can activate the glucagon gene promoter through G1, their relative importance in vivo is unknown. We first studied the expression of Maf-B, c-Maf, and Cdx-2/3 in the developing and adult mouse pancreas. Although Maf-B was detectable in a progressively increasing number of α-cells throughout development and in adulthood, c-Maf and Cdx-2/3 were expressed at low and very low levels, respectively. However, c-Maf but not Cdx-2/3 was detectable in adult islets by Western blot analyses. We then demonstrated the in vivo interactions of Pax-6, Cdx-2/3, Maf-B, and c-Maf but not Brain-4 with the glucagon gene promoter in glucagon-producing cells. Although Pax-6, Cdx-2/3, Maf-B, and c-Maf were all able to bind G1 by themselves, we showed that Pax-6 could interact with Maf-B, c-Maf, and Cdx-2/3 and activate transcription of the glucagon gene promoter. Overexpression of dominant negative forms of Cdx-2/3 and Mafs in α-cell lines indicated that Cdx-2/3 and the Maf proteins interact on an overlapping site within G1 and that this binding site is critical in the activation of the glucagon gene promoter. Finally, we show that specific inhibition of Pax-6 and c-Maf but not Cdx-2/3 or Maf-B led to decreases in endogenous glucagon gene expression and that c-Maf binds the glucagon gene promoter in mouse islets. We conclude that Pax-6 and c-Maf interact with G1 to activate basal expression of the glucagon gene. Specific expression of the glucagon gene in the rat pancreas requires the presence of the G1 element localized at -100/-49 base pairs on the promoter. Although it is known that multiple transcription factors such as Pax-6, Cdx-2/3, c-Maf, Maf-B, and Brain-4 can activate the glucagon gene promoter through G1, their relative importance in vivo is unknown. We first studied the expression of Maf-B, c-Maf, and Cdx-2/3 in the developing and adult mouse pancreas. Although Maf-B was detectable in a progressively increasing number of α-cells throughout development and in adulthood, c-Maf and Cdx-2/3 were expressed at low and very low levels, respectively. However, c-Maf but not Cdx-2/3 was detectable in adult islets by Western blot analyses. We then demonstrated the in vivo interactions of Pax-6, Cdx-2/3, Maf-B, and c-Maf but not Brain-4 with the glucagon gene promoter in glucagon-producing cells. Although Pax-6, Cdx-2/3, Maf-B, and c-Maf were all able to bind G1 by themselves, we showed that Pax-6 could interact with Maf-B, c-Maf, and Cdx-2/3 and activate transcription of the glucagon gene promoter. Overexpression of dominant negative forms of Cdx-2/3 and Mafs in α-cell lines indicated that Cdx-2/3 and the Maf proteins interact on an overlapping site within G1 and that this binding site is critical in the activation of the glucagon gene promoter. Finally, we show that specific inhibition of Pax-6 and c-Maf but not Cdx-2/3 or Maf-B led to decreases in endogenous glucagon gene expression and that c-Maf binds the glucagon gene promoter in mouse islets. We conclude that Pax-6 and c-Maf interact with G1 to activate basal expression of the glucagon gene. The glucagon gene is expressed in the α-cells of the pancreatic islets, the L cells of the intestine, and specific areas of the brain (1Philippe J. Endocr. Rev. 1991; 12: 252-271Crossref PubMed Scopus (73) Google Scholar). Although multiple transcription factors have been proposed to regulate glucagon gene transcription, the molecular mechanisms by which glucagon gene expression is restricted to α-cells are still not known. Pancreas-specific expression of the glucagon gene is conferred by the islet-specific enhancer elements G2, G3, and G4 (2Philippe J. Drucker D.J. Knepel W. Jepeal L. Misulovin Z. Habener J.F. Mol. Cell Biol. 1988; 8: 4877-4888Crossref PubMed Scopus (116) Google Scholar, 3Philippe J. Proc. Natl. Acad. Sci. U. S. A. 1991; 88: 7224-7227Crossref PubMed Scopus (99) Google Scholar, 4Philippe J. Morel C. Cordier-Bussat M. J. Biol. Chem. 1995; 270: 3039-3045Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar, 5Cordier-Bussat M. Morel C. Philippe J. Mol. Cell Biol. 1995; 15: 3904-3916Crossref PubMed Scopus (31) Google Scholar), whereas the proximal promoter element G1 is critical for α-cell-specific expression (2Philippe J. Drucker D.J. Knepel W. Jepeal L. Misulovin Z. Habener J.F. Mol. Cell Biol. 1988; 8: 4877-4888Crossref PubMed Scopus (116) Google Scholar, 3Philippe J. Proc. Natl. Acad. Sci. U. S. A. 1991; 88: 7224-7227Crossref PubMed Scopus (99) Google Scholar, 4Philippe J. Morel C. Cordier-Bussat M. J. Biol. Chem. 1995; 270: 3039-3045Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar, 6Morel C. Cordier-Bussat M. Philippe J. J. Biol. Chem. 1995; 270: 3046-3055Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 7Laser B. Meda P. Constant I. Philippe J. J. Biol. Chem. 1996; 271: 28984-28994Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar). We and others have proposed Pax-6, Cdx-2/3, large Mafs, Brain-4, and Foxa-2 as potential factors implicated in glucagon gene expression through the transactivation of the G1 element in glucagon-producing cells by transfection studies (8Jin T. Drucker D.J. Mol. Cell Biol. 1996; 16: 19-28Crossref PubMed Scopus (114) Google Scholar, 9Planque N. Leconte L. Coquelle F.M. Benkhelifa S. Martin P. Felder-Schmittbuhl M.P. Saule S. J. Biol. Chem. 2001; 276: 35751-35760Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar, 10Hussain J. Habener J.F. Mol. Cell Biol. PubMed Google Scholar, M. A. B. Philippe J. Mol. 16: PubMed Scopus Google Scholar). However, the and relative importance of factors in vivo is unknown. Pax-6 been to expressed in the pancreas and pancreas development as as and in the adult N. S. C. Saule S. Mol. 8: PubMed Scopus Google Scholar, L. B. A. P. PubMed Scopus Google Scholar). Pax-6 is critical for α-cell development and glucagon gene promoter through the enhancer element and the α-cell-specific element G1 J. Morel C. Cordier-Bussat M. J. Biol. Chem. 1995; 270: 3039-3045Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar). Pax-6 is for the transactivation of glucagon gene promoter in the and large Drucker D.J. Mol. PubMed Google Scholar). Pax-6 is expressed in all pancreatic cells and the of glucagon gene Pax-6 been to interact with Cdx-2/3 and in a transactivation of the glucagon gene N. Leconte L. Coquelle F.M. Benkhelifa S. Martin P. Felder-Schmittbuhl M.P. Saule S. J. Biol. Chem. 2001; 276: 35751-35760Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar, B. A. N. Saule S. Philippe J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). We and others have that Cdx-2/3 is able to a with Pax-6 on the G1 element glucagon-producing and gene transcription by transfection B. A. N. Saule S. Philippe J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). the expression of Cdx-2/3 in α-cells is not Although Cdx-2/3 been to in α-cells of the adult mouse pancreas by A. J. Mol. Cell PubMed Scopus Google Scholar), it is the adult rat and α-cells as as J. Habener J.F. Mol. Cell Biol. PubMed Google Scholar, S. S. C. PubMed Scopus Google Scholar). the expression of the large Mafs in the α-cells is Although is expressed in pancreatic L. I. A. Mol. Cell Biol. PubMed Scopus Google Scholar, S. J. Mol. PubMed Scopus (61) Google Scholar), the expression of Maf-B and c-Maf in and glucagon-producing cells been by I. J. L. B. PubMed Scopus Google that Maf-B is expressed in mouse and development but in α-cells in the adult islets, whereas c-Maf is not expressed at have that c-Maf but not Maf-B is expressed in α-cells S. J. Mol. PubMed Scopus (61) Google Scholar). or show an in and cells throughout a of Maf-B and c-Maf in of cells I. B. M. T. S. M. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar, W. T. I. I. S. A. Scholar). Brain-4 and have been to activate glucagon gene expression and to expressed in the Brain-4 is expressed in α-cells throughout development and in the adult and been proposed as a for α-cell specific expression of the glucagon gene J. Habener J.F. Mol. Cell Biol. PubMed Google Scholar, A. A. P. Biol. PubMed Scopus Google Brain-4 have and of the the of Brain-4 in glucagon gene expression A. A. P. Biol. PubMed Scopus Google Scholar). and Foxa-2 have been proposed to regulate glucagon gene expression by binding to G1 and of the rat glucagon promoter M. A. B. Philippe J. Mol. 16: PubMed Scopus Google Scholar). the binding site of and on G1 is overlapping with Pax-6, and of factors in α-cells in an inhibition of expression of the glucagon an for factors on The of this was to and the transcription factors with G1 in the α-cell-specific expression of the glucagon gene. We show by that Pax-6, Cdx-2/3, Maf-B, and c-Maf interact with the glucagon gene promoter in whereas Pax-6, Maf-B and c-Maf in that Cdx-2/3 Brain-4 are for glucagon gene whereas Maf-B and c-Maf are expressed in the islets, Cdx-2/3 is expressed at very low in the mouse and the is not by or Western blot analyses. Pax-6 and c-Maf are the of the glucagon gene promoter with or We show by the expression of c-Maf, Maf-B, and Cdx-2/3 by that c-Maf to the critical of Pax-6 to activate endogenous glucagon gene Finally, we that c-Maf with the glucagon gene promoter in adult mouse islets, of c-Maf on glucagon gene transcription in Cell glucagon-producing J. S. M. A. PubMed Scopus Google and cells S. S. Habener J.F. PubMed Scopus Google as as the lines were in with and of and of and was mouse and adult mouse intestine, and lines to the of was with and as by the mouse pancreas and lines were by as by the were on were for glucagon and gene expression in glucagon-producing lines and a was with of was in and of the was by of the of the and by the and with the The were the The were by pancreatic islets were as P. Meda P. J. PubMed Google Scholar, J. I. Meda P. PubMed Scopus Google Scholar). Western were as P. 1988; Full Text PDF PubMed Scopus Google Scholar, P. W. J. 1988; PubMed Scopus Google or cells. to of were on a and to was with to Pax-6 S. Cdx-2/3 M. of Maf-B or c-Maf and with The was with was by of were with c-Maf was with or c-Maf of c-Maf was for at with of specific c-Maf and Western cells were and in a to a on the cells were by the of and were by and with a of was to the and for proteins were by of were at with a mouse to The were then with and in of of and of the of were on and on to The were with Pax-6 or Maf-B and c-Maf and with to were a of adult or mouse pancreas with were with and glucagon with Maf-B and Cdx-2/3 Maf-B and Cdx-2/3 were with The of of glucagon and Maf-B were with the The were on at and to cells in to pancreas to at all cells were by the PubMed Scopus Google as B. A. N. Saule S. Philippe J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). and lines were by the PubMed Scopus Google Scholar, D.J. Philippe J. Jepeal L. Habener J.F. J. Biol. Chem. Full Text PDF PubMed Google for glucagon promoter the dominant negative forms of and Cdx-2/3 were in and cells the to the promoter transactivation was studied transfection of to base of the of the rat glucagon promoter in and glucagon promoter were by as J. M. J. Biol. Chem. Full Text PDF PubMed Google Scholar). The cells were with a the gene or the gene by the to transfection of and forms was with a and were by and respectively. of were of in were the to of the of rat glucagon promoter to the G1 element and cells mouse Pax-6 in the Cdx-2/3 by M. of mouse Maf-B, or mouse c-Maf proteins by respectively. of of and of as M. Morel C. Philippe J. Mol. Cell Biol. 1995; 15: 3904-3916Crossref PubMed Scopus (31) Google with of and of and were by S. Saule and M. of respectively. and were at were to PubMed Scopus Google Scholar). were and cells and by and or mouse of were first with for the were at with of of and as as The were to of at and in a low and in as by L. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). were in the presence of by at the was in and as a for The of for of binding on the glucagon gene proximal promoter to in cells were and the of for cells and mouse adult islets were and and and were on and by a specific of were by for Cdx-2/3 and by for Maf-B, c-Maf, and Pax-6 were at the of to Pax-6, Maf-B, c-Maf, and Cdx-2/3 cells in were with of of as by the The were and were transfection as are as the and by of was to Specific expression of the glucagon gene in rat pancreas requires the presence of the G1 which binding for Pax-6, Cdx-2/3, Mafs, and Brain-4 the expression of Pax-6 and Brain-4 in α-cells been pancreas development and J. Habener J.F. Mol. Cell Biol. PubMed Google Scholar, L. B. A. P. PubMed Scopus Google Scholar, A. A. P. Biol. PubMed Scopus Google Scholar), we studied the expression of Cdx-2/3, Maf-B, and c-Maf, which have all been proposed to activate glucagon gene transcription with We first the expression of Cdx-2/3, Maf-B, and c-Maf at of pancreatic development in Maf-B and c-Maf can at the adult all Maf-B are with of The development to in the Mafs are in the and mouse glucagon-producing lines and respectively. Cdx-2/3 was mouse pancreas development and in the adult islets, of the a specific Cdx-2/3 the presence of Cdx-2/3 at all the not However, we Cdx-2/3 in cells but not in cells. We then on mouse pancreas at and and in the adult We could not Cdx-2/3 at of in the whereas it was in the adult mouse intestine, as a Cdx-2/3 was not by Western blot of adult whereas it was in cells not We for the presence of the transcription Maf-B in cells Maf-B is as as and can the adult of the cells expressed progressively the adult to c-Maf, we and the was mouse c-Maf and to whereas was not specific it could Maf-B and proteins not and S. J. Mol. PubMed Scopus (61) Google Scholar). However, we could not c-Maf in pancreas the specific as by others L. I. A. Mol. Cell Biol. PubMed Scopus Google Scholar, I. J. L. B. PubMed Scopus Google Scholar). the presence of c-Maf and Maf-B in we Western of α-cell lines and adult mouse Mafs were in cells and adult islets, whereas Maf-B was in cells and We that the mouse c-Maf is not able to c-Maf by Western that Cdx-2/3 is not and for glucagon gene expression it is cells and not or very expressed in mouse pancreas development and in the we a of Cdx-2/3 at of development in glucagon gene Maf-B and c-Maf are expressed throughout development and in the adult a of glucagon-producing cells not the large Mafs at factors not for glucagon gene it is that low of large Mafs by are in all the of Pax-6, Cdx-2/3, Maf-B, and c-Maf on glucagon gene we first on lines to the in vivo binding of transcription factors to the glucagon promoter We the binding of Brain-4, an α-cell-specific transcription in and cells that been proposed to bind G1 J. Habener J.F. Mol. Cell Biol. PubMed Google Scholar). the Pax-6, Maf-B, c-Maf, and Cdx-2/3 were to interact with the glucagon promoter but not Brain-4 were with cells of Cdx-2/3 was in with the that it is not expressed in cells. that Pax-6, Maf-B, and c-Maf interact with G1 as as Cdx-2/3 in cells but not the of Pax-6, Cdx-2/3, and large Mafs on the glucagon gene we with the rat glucagon gene promoter to the gene with expression of transcription factors in the We first the of Maf-B, c-Maf, and Cdx-2/3 in for of Maf-B and c-Maf were but of Cdx-2/3 not Pax-6, Cdx-2/3, Maf-B, and c-Maf can all activate glucagon gene promoter by and respectively. Cdx-2/3 and have been proposed to interact with Pax-6, we transfection studies with Pax-6, Cdx-2/3, and the large Mafs in Pax-6 and Cdx-2/3, Pax-6 and Maf-B, or Pax-6 and c-Maf were we a activation on glucagon gene promoter and was with the of all we or Cdx-2/3 and Maf-B or of the with or Maf not glucagon gene promoter transactivation that c-Maf is a of the glucagon gene promoter with Maf-B or Cdx-2/3 and the activation with However, that of Cdx-2/3 are of Maf-B and c-Maf, it is that the and have the binding of Pax-6, Cdx-2/3, and the large Mafs to G1 as as their we with the G1 element of the rat glucagon gene promoter and cells the Pax-6, Cdx-2/3, or the large Maf proteins Pax-6 and Cdx-2/3 were able to bind the G1 element and as by the Pax-6 or Cdx-2/3 proteins Maf-B and c-Maf were able to interact with G1 cells Pax-6 were to the Maf-B or c-Maf, with the of Maf-B, c-Maf, Pax-6 proteins were The with and were by the that Maf-B and c-Maf can interact with Pax-6 on Maf-B and c-Maf can interact with Pax-6 of binding as by We then the binding of Pax-6, Cdx-2/3, Maf-B, and c-Maf or in on G1 We G1 with a of Pax-6, Cdx-2/3, Maf-B, or c-Maf and increasing of G1 Pax-6 the whereas Cdx-2/3 the for large Mafs an We then the relative binding of the of and for G1 the relative low of Cdx-2/3 for G1, the with that Pax-6 or in with Cdx-2/3 the for G1, that Cdx-2/3, at low levels, still a in glucagon gene transcription to the of Cdx-2/3 and Maf proteins on glucagon gene we dominant negative forms of proteins and T. and and that bind G1 as as the forms not binds G1 as as Maf-B and c-Maf, we for dominant negative to for Maf-B or c-Maf We in cells of the of the rat glucagon gene promoter to the gene and expression Pax-6, Cdx-2/3, Maf-B, or the dominant negative forms of Cdx-2/3 and and were able to the with Pax-6 and Cdx-2/3 or was able to Maf on glucagon promoter as as whereas was able to that forms can with and Mafs for binding We then the of and on glucagon gene promoter in the lines were the rat glucagon promoter and or We in lines an inhibition of with dominant negative factors and in and with and and in cells with the of Cdx-2/3 in of in a inhibition of glucagon promoter large Mafs and Cdx-2/3 binding to G1 of the Maf We the of and on endogenous glucagon gene expression in cells Overexpression of negative of Cdx-2/3 and led to a of glucagon of and of dominant negative forms of Cdx-2/3 and large Mafs on glucagon gene promoter in glucagon-producing cells. and lines were with of and of or expression The are expressed relative to the gene. cells were with of and expression glucagon are expressed relative to the and for of the are as the for transfection The with a the of Pax-6, the large Mafs and Cdx-2/3 on glucagon gene we to the expression of Pax-6, Cdx-2/3, Maf-B, and c-Maf in of the transfection of specific led to decreases of Pax-6, Cdx-2/3, Maf-B, and c-Maf in cells of and and Pax-6, Cdx-2/3, and Maf-B proteins were by and as by Western However, c-Maf was not with the c-Maf as We then endogenous glucagon gene expression in cells of Pax-6 expression led to a of endogenous glucagon gene expression specific of Cdx-2/3 not glucagon gene that Cdx-2/3 is not on basal glucagon gene transcription in of c-Maf expression led to a in glucagon levels, whereas inhibition of Maf-B was not by that c-Maf but not Maf-B is in the of basal glucagon gene expression in cells. Finally, we of and that inhibition of glucagon gene expression in the presence of Pax-6 or c-Maf and that inhibition of Pax-6 and c-Maf not to Finally, to c-Maf on glucagon gene expression in we c-Maf binding in mouse adult islets by of glucagon gene promoter we show that c-Maf with the glucagon gene promoter in vivo We conclude that Pax-6 and c-Maf are able to bind the glucagon gene promoter and are critical for basal glucagon gene We show that Pax-6 and c-Maf are the to the glucagon gene promoter through is on a of expression and G1 is a large element with potential binding a site to which Pax-6 and Brain-4 have been to and proximal for Cdx-2/3 and the large The binding for Pax-6 and Brain-4 are overlapping J. Habener J.F. Mol. Cell Biol. PubMed Google Scholar, B. A. N. Saule S. Philippe J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). Pax-6 is in glucagon-producing cells of the mouse pancreas at and in all pancreatic cells at in development N. S. C. Saule S. Mol. 8: PubMed Scopus Google Scholar, L. B. A. P. PubMed Scopus Google Scholar, M. A. J. Martin PubMed Scopus Google Scholar). Pax-6 with G1 and the rat glucagon gene promoter and with Cdx-2/3 and the large Mafs N. Leconte L. Coquelle F.M. Benkhelifa S. Martin P. Felder-Schmittbuhl M.P. Saule S. J. Biol. Chem. 2001; 276: 35751-35760Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar, B. A. N. Saule S. Philippe J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). Brain-4 is expressed in the developing and adult α-cells and is able to activate glucagon gene promoter through G1 J. Habener J.F. Mol. Cell Biol. PubMed Google Scholar, P. T. Z. T. PubMed Scopus Google Scholar). Brain-4 is expressed in α-cells and not in However, by to the in Pax-6 α-cells are the of Brain-4 in not in in α-cell development or A. A. P. Biol. PubMed Scopus Google Scholar), that Pax-6 is a Brain-4 in the activation of the α-cell-specific element with this we by that Pax-6 but not Brain-4 in vivo with G1, whereas factors are in cells. the of Pax-6 in glucagon gene expression is by the in endogenous glucagon in the presence of Pax-6 gene We conclude that Pax-6 binds the binding site of G1 and is critical for glucagon gene Cdx-2/3 and the large Mafs have been proposed to interact on the G1 element and to activate glucagon gene with Pax-6 (8Jin T. Drucker D.J. Mol. Cell Biol. 1996; 16: 19-28Crossref PubMed Scopus (114) Google Scholar, 9Planque N. Leconte L. Coquelle F.M. Benkhelifa S. Martin P. Felder-Schmittbuhl M.P. Saule S. J. Biol. Chem. 2001; 276: 35751-35760Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar, B. A. N. Saule S. Philippe J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). binding are but it is not known their are overlapping and their binding is their on endogenous glucagon gene expression not been studies have been B. Meda P. Constant I. Philippe J. J. Biol. Chem. 1996; 271: 28984-28994Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar, S. J. Mol. PubMed Scopus (61) Google Scholar, I. J. L. B. PubMed Scopus Google Scholar, Habener J.F. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, J. P. PubMed Scopus Google Scholar). Cdx-2/3, is to a critical in glucagon gene studies show that the Cdx-2/3 gene is expressed at very low in the developing pancreas and in the adult islets. it is by it been in the adult rat and α-cells as as in S. S. C. PubMed Scopus Google Scholar). We that in the Cdx-2/3 gene is not expressed that it is for glucagon gene Finally, Cdx-2/3 gene expression in cells not in in glucagon levels, the that Cdx-2/3 can bind to the glucagon gene promoter as by analyses. The the of Cdx-2/3 to bind the glucagon promoter in vivo and the of it is We that Cdx-2/3 is expressed at very low in α-cells and to a in glucagon gene The large Maf multiple Maf-B, c-Maf, and Although been to expressed in cells L. I. A. Mol. Cell Biol. PubMed Scopus Google Scholar, S. J. Mol. PubMed Scopus (61) Google Scholar), on the of Maf-B and c-Maf in and was first that Maf-B was expressed in and c-Maf was at low L. I. A. Mol. Cell Biol. PubMed Scopus Google Scholar). Maf-B and c-Maf were then to expressed in pancreatic α-cell lines and c-Maf to specific for α-cells in the mouse S. J. Mol. PubMed Scopus (61) Google Scholar). that Maf-B is expressed as as and in mouse and cells not and restricted to α-cells in the adult and a I. J. L. B. PubMed Scopus Google Scholar, W. T. T. I. S. A. Biol. PubMed Scopus Google Scholar). is to that in the Maf-B is expressed in cells in the c-Maf by is in development and in the adult in the mouse W. T. T. I. S. A. Biol. PubMed Scopus Google and pancreas M. S. A. M. PubMed Scopus Google Scholar), it been proposed that c-Maf is not expressed in pancreatic cells I. J. L. B. PubMed Scopus Google Scholar). We that Maf-B is expressed at c-Maf mouse pancreatic development and in the The is in glucagon-producing We could not the presence and of c-Maf by the were or not by Western blot the demonstrated the presence of c-Maf in a of in cells and mouse adult islets W. T. T. I. S. A. Biol. PubMed Scopus Google Scholar). Maf-B and c-Maf are able to bind G1 in and in vivo as indicated by and bind with the and in with Maf-B and c-Maf can interact with Pax-6 in the presence or of G1 as by and an Pax-6 and the large Mafs was for N. Leconte L. Coquelle F.M. Benkhelifa S. Martin P. Felder-Schmittbuhl M.P. Saule S. J. Biol. Chem. 2001; 276: 35751-35760Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar). The of c-Maf with Maf-B in the presence or of Pax-6, that the large Mafs have have been for the gene promoter A. J. Mol. Biol. PubMed Scopus Google Scholar). of c-Maf but not Maf-B in cells endogenous glucagon levels, that factors not at in glucagon We the that are by the that a inhibition of the Maf-B not to glucagon gene whereas the in c-Maf that is expressed at low in in the Maf-B was to for the of We that by to the in the Pax-6 the activate c-Maf gene with c-Maf in activate glucagon gene expression A. J. Mol. Biol. PubMed Scopus Google Scholar). then and the of Maf-B, which is in the mouse α-cells c-Maf and which is able to bind the glucagon gene promoter in vivo at I. B. M. T. S. M. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). Maf-B implicated in in the and not basal glucagon gene of or showed a of large Mafs in the of and I. B. M. T. S. M. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar, W. T. I. I. S. A. Scholar). Maf-B is able to through and with c-Maf, Mafs, and M. M. Mol. Cell Biol. PubMed Scopus Google Scholar), a potential in the expression of the glucagon gene. to is that Maf-B can activate glucagon gene transcription in vivo a showed that inhibition of Maf-B expression in cells not to a of the rat glucagon promoter S. J. Mol. PubMed Scopus (61) Google Scholar), to the of a showed that of specific c-Maf in mouse led to a in glucagon gene that c-Maf can the glucagon gene expression M. A. A. T. S. Scholar). We show that c-Maf is in basal glucagon gene expression in cells and is able to bind the glucagon gene promoter in mouse pancreatic islets the and are we the of dominant negative forms of the large Mafs or Cdx-2/3 on glucagon gene transcription in and cells. Overexpression of and glucagon promoter and glucagon gene expression in cells. We in which not Cdx-2/3, that the large and are overlapping and that is the large Mafs and Cdx-2/3 to bind the critical importance of the and proximal elements of G1 for glucagon gene Although c-Maf is expressed in it is in as as We proposed the that glucagon gene expression a (1Philippe J. Endocr. Rev. 1991; 12: 252-271Crossref PubMed Scopus (73) Google Scholar). The of the transcription such as and through the of and factors development for the glucagon gene to expressed and for the of the α-cell in the presence of islet-specific The of the factors or in in an in α-cells and a large number of cells glucagon and B. M. P. PubMed Scopus Google Scholar, U. J. L. 12: PubMed Scopus Google Scholar). We have that expression of or in glucagon-producing lines basal transcription of the glucagon gene promoter by and are able to bind to the site with or with expression of in glucagon-producing cells endogenous glucagon gene expression B. A. A. Philippe J. PubMed Scopus Google Scholar, B. A. A. T. P. Philippe J. PubMed Scopus Google Scholar). Finally, of a dominant negative of in cells to of and glucagon in the an for on glucagon gene expression P. B. Philippe J. J. Biol. Chem. 2001; 276: Full Text Full Text PDF PubMed Scopus Google Scholar). been to an on glucagon gene expression S. M. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google through with Pax-6 A. Philippe J. J. PubMed Scopus Google Scholar). We conclude that α-cell-specific expression of the glucagon gene is conferred by potential the of Pax-6 and c-Maf on G1 and the of specific transcription factors such as and We S. Saule for Pax-6 and T. of Cell and of and of and for the dominant negative forms of Cdx-2/3 and respectively. We I. of and of for in
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Gosmain et al. (2007) studied this question.
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