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Pancreatic beta cell-specific transcription of the pdx-1 gene. The role of conserved upstream control regions and their hepatic nuclear factor 3beta sites 总被引:10,自引:0,他引:10
Gerrish K Gannon M Shih D Henderson E Stoffel M Wright CV Stein R 《The Journal of biological chemistry》2000,275(5):3485-3492
To identify potential transactivators of pdx-1, we sequenced approximately 4.5 kilobases of the 5' promoter region of the human and chicken homologs, assuming that sequences conserved with the mouse gene would contain critical cis-regulatory elements. The sequences associated with hypersensitive site 1 (HSS1) represented the principal area of homology within which three conserved subdomains were apparent: area I (-2694 to -2561 base pairs (bp)), area II (-2139 to -1958 bp), and area III (-1879 to -1799 bp). The identities between the mouse and chicken/human genes are very high, ranging from 78 to 89%, although only areas I and III are present within this region in chicken. Pancreatic beta cell-selective expression was shown to be controlled by mouse and human area I or area II, but not area III, from an analysis of pdx-1-driven reporter activity in transfected beta- and non-beta cells. Mutational and functional analyses of conserved hepatic nuclear factor 3 (HNF3)-like sites located within area I and area II demonstrated that activation by these regions was mediated by HNF3beta. To determine if a similar regulatory relationship might exist within the context of the endogenous gene, pdx-1 expression was measured in embryonic stem cells in which one or both alleles of HNF3beta were inactivated. pdx-1 mRNA levels induced upon differentiation to embryoid bodies were down-regulated in homozygous null HNF3beta cells. Together, these results suggest that the conserved sequences represented by areas I and II define the binding sites for factors such as HNF3beta, which control islet beta cell-selective expression of the pdx-1 gene. 相似文献
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Conserved transcriptional regulatory domains of the pdx-1 gene 总被引:11,自引:0,他引:11
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The islet beta cell-enriched RIPE3b1/Maf transcription factor regulates pdx-1 expression 总被引:3,自引:0,他引:3
Samaras SE Zhao L Means A Henderson E Matsuoka TA Stein R 《The Journal of biological chemistry》2003,278(14):12263-12270
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Functional conservation of regulatory elements in the pdx-1 gene: PDX-1 and hepatocyte nuclear factor 3beta transcription factors mediate beta-cell-specific expression 总被引:3,自引:0,他引:3
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Marshak S Benshushan E Shoshkes M Havin L Cerasi E Melloul D 《Molecular and cellular biology》2000,20(20):7583-7590
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FoxA2, Nkx2.2, and PDX-1 regulate islet beta-cell-specific mafA expression through conserved sequences located between base pairs -8118 and -7750 upstream from the transcription start site
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Raum JC Gerrish K Artner I Henderson E Guo M Sussel L Schisler JC Newgard CB Stein R 《Molecular and cellular biology》2006,26(15):5735-5743
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Neurogenin3 and hepatic nuclear factor 1 cooperate in activating pancreatic expression of Pax4 总被引:3,自引:0,他引:3
Smith SB Gasa R Watada H Wang J Griffen SC German MS 《The Journal of biological chemistry》2003,278(40):38254-38259
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