A mutational analysis of the insulin gene transcription control region: expression in beta cells is dependent on two related sequences within the enhancer - PubMed (original) (raw)
A mutational analysis of the insulin gene transcription control region: expression in beta cells is dependent on two related sequences within the enhancer
O Karlsson et al. Proc Natl Acad Sci U S A. 1987 Dec.
Abstract
Cell-specific expression of the insulin gene is controlled by cis-acting DNA sequences located within approximately equal to 350 base pairs of the 5' flanking DNA immediately upstream from the transcription start site. Using synthetic oligonucleotides, we have constructed a systematic series of block replacement mutants spanning this region. No single sequence appears to be absolutely required for expression. However, three of the mutants exhibit 5-10 times less activity and several others show 2-3 times less. Simultaneous mutation of two of the most mutationally sensitive regions leads to virtual abolition of activity. These two elements are structurally related and presumably represent key components of the machinery determining the cell-specific expression of the insulin gene.
Similar articles
- Pancreatic beta-cell-type-specific expression of the rat insulin II gene is controlled by positive and negative cellular transcriptional elements.
Whelan J, Poon D, Weil PA, Stein R. Whelan J, et al. Mol Cell Biol. 1989 Aug;9(8):3253-9. doi: 10.1128/mcb.9.8.3253-3259.1989. Mol Cell Biol. 1989. PMID: 2552288 Free PMC article. - The Pan basic helix-loop-helix proteins are required for insulin gene expression.
Vierra CA, Nelson C. Vierra CA, et al. Mol Endocrinol. 1995 Jan;9(1):64-71. doi: 10.1210/mend.9.1.7760851. Mol Endocrinol. 1995. PMID: 7760851 - Molecular mechanisms of cAMP-regulated gene expression.
Walton KM, Rehfuss RP. Walton KM, et al. Mol Neurobiol. 1990 Fall-Winter;4(3-4):197-210. doi: 10.1007/BF02780341. Mol Neurobiol. 1990. PMID: 1966918 Review. - Regulation of insulin gene transcription by nutrients.
Docherty K, Macfarlane WM, Read ML, Smith SB, Wilson ME, Bujalska I, Gilligan M. Docherty K, et al. Biochem Soc Trans. 1996 May;24(2):368-72. doi: 10.1042/bst0240368. Biochem Soc Trans. 1996. PMID: 8736765 Review. No abstract available.
Cited by
- PDX-1: A Promising Therapeutic Target to Reverse Diabetes.
Zhang Y, Fang X, Wei J, Miao R, Wu H, Ma K, Tian J. Zhang Y, et al. Biomolecules. 2022 Nov 30;12(12):1785. doi: 10.3390/biom12121785. Biomolecules. 2022. PMID: 36551213 Free PMC article. Review. - Role of the Transcription Factor MAFA in the Maintenance of Pancreatic β-Cells.
Nishimura W, Iwasa H, Tumurkhuu M. Nishimura W, et al. Int J Mol Sci. 2022 Apr 19;23(9):4478. doi: 10.3390/ijms23094478. Int J Mol Sci. 2022. PMID: 35562869 Free PMC article. Review. - In vivo evaluation of GG2-GG1/A2 element activity in the insulin promoter region using the CRISPR-Cas9 system.
Noguchi H, Miyagi-Shiohira C, Kinjo T, Saitoh I, Watanabe M. Noguchi H, et al. Sci Rep. 2021 Oct 13;11(1):20290. doi: 10.1038/s41598-021-99808-6. Sci Rep. 2021. PMID: 34645928 Free PMC article. - SIX2 and SIX3 coordinately regulate functional maturity and fate of human pancreatic β cells.
Bevacqua RJ, Lam JY, Peiris H, Whitener RL, Kim S, Gu X, Friedlander MSH, Kim SK. Bevacqua RJ, et al. Genes Dev. 2021 Feb 1;35(3-4):234-249. doi: 10.1101/gad.342378.120. Epub 2021 Jan 14. Genes Dev. 2021. PMID: 33446570 Free PMC article. - A novel function of Onecut1 protein as a negative regulator of MafA gene expression.
Yamamoto K, Matsuoka TA, Kawashima S, Takebe S, Kubo F, Miyatsuka T, Kaneto H, Shimomura I. Yamamoto K, et al. J Biol Chem. 2013 Jul 26;288(30):21648-58. doi: 10.1074/jbc.M113.481424. Epub 2013 Jun 17. J Biol Chem. 2013. PMID: 23775071 Free PMC article.
References
- EMBO J. 1983;2(8):1373-8 - PubMed
- Diabetes Res. 1987 Mar;4(3):103-7 - PubMed
- Cell. 1979 Oct;18(2):533-43 - PubMed
- Nucleic Acids Res. 1981 Jul 10;9(13):2989-98 - PubMed
- Proc Natl Acad Sci U S A. 1981 Jul;78(7):4339-43 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical