Repression of insulin gene transcription by indirect genomic signaling via the estrogen receptor in pancreatic beta cells

In Vitro Cellular & Developmental Biology. Animal
Takashi SekidoMitsuhisa Komatsu

Abstract

The mechanism whereby 17β-estradiol (E2) mediates insulin gene transcription has not been fully elucidated. In this study, exposure of hamster insulinoma (HIT-T15) cells to 5 × 10-9 to 1 × 10-7 M E2 led to a concentration-dependent decrease of insulin mRNA levels. Transient expression of the estrogen receptor (ER) in HIT-T15 cells revealed that estrogen receptor α (ERα) repressed transcription of the rat insulin II promoter in both ligand-dependent and ligand-independent manners. The N-terminal A/B domain of ERα was not required for either activity. However, the repression was absent with mutated ER lacking the DNA-binding domain. Moreover, introducing mutations in the D-box and P-box of the zinc finger of ER (C227S, C202L) also abolished the repression. Deletion of the insulin promoter region revealed that nucleotide positions - 238 to - 144 (relative to the transcriptional start site) were needed for ER repression of the rat insulin II gene. PDX1- and BETA2-binding sites were required for the repression, but an estrogen response element-like sequence or an AP1 site in the promoter was not involved. In conclusion, we found that estrogen repressed insulin mRNA expression in a beta cell line. In addition, the ER suppressed insul...Continue Reading

References

Jun 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·A Voronova, D Baltimore
Oct 1, 1996·Molecular Endocrinology·K B HorwitzL Tung
Mar 27, 2001·Biochemical and Biophysical Research Communications·T MiyamotoK Hashizume
Mar 30, 2001·The Journal of Biological Chemistry·M JakackaJ L Jameson
Oct 3, 2001·Physiological Reviews·S NilssonJ A Gustafsson
Nov 26, 2003·Biochemical and Biophysical Research Communications·Takahiro SakumaKiyoshi Hashizume
Feb 8, 2005·Molecular Endocrinology·Linda Björnström, Maria Sjöberg
Sep 30, 2005·Diabetologia·I F Godsland
Jun 7, 2006·Proceedings of the National Academy of Sciences of the United States of America·Cedric Le MayFranck Mauvais-Jarvis
Oct 24, 2006·Biochemical and Biophysical Research Communications·Wei JiangKiyoshi Hashizume
Jun 21, 2007·American Journal of Physiology. Endocrinology and Metabolism·Tomasz Szkudelski
Jul 7, 2007·Physiological Reviews·Nina HeldringJan-Ake Gustafsson
May 1, 2008·PloS One·Paloma Alonso-MagdalenaAngel Nadal
Aug 19, 2009·The Journal of Physiology·Angel NadalIvan Quesada
Jul 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Winifred P S WongFranck Mauvais-Jarvis
Feb 15, 2012·Nature Reviews. Endocrinology·Joseph P Tiano, Franck Mauvais-Jarvis
Mar 6, 2013·Endocrine Reviews·Franck Mauvais-JarvisAndrea L Hevener
Oct 30, 2014·Biochemia Medica·Peter VrtačnikJanja Marc
May 15, 2015·The Journal of Endocrinology·Min Kyong MoonKyong Soo Park
Aug 5, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jie WeiYi Lin

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Methods Mentioned

BETA
PCR
pull-down
transfection
electrophoresis
electrophoretic mobility shift

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