A Smad-binding element in intron 1 participates in activin-dependent regulation of the follistatin gene

The Journal of Biological Chemistry
Amy L BlountLouise M Bilezikjian

Abstract

Follistatins exert critical autocrine or paracrine control in many tissues by binding and bio-neutralizing activin and several other transforming growth factor-beta ligands. In the pituitary, activin acts locally to induce follistatin expression and thus modulate its own actions. This local feedback loop safeguards against excessive activin signaling and maintains the necessary balance of activin and follistatin tone. To better understand the mechanisms underlying the activation of follistatin by activin A, follistatin transcription was evaluated in gonadotrope-derived alphaT3-1 cells. Transient transfection experiments established that follistatin-luciferase plasmids that incorporate up to 2.86 kb of the upstream region of the rat follistatin gene are not induced by activin A in alphaT3-1 cells. On the other hand, plasmids that incorporate intron 1 are responsive to activin A and induced by a constitutively active form of ALK4. These experiments ultimately identified a conserved Smad-binding element (SBE1) in intron 1, between +1791 and +1795. In alphaT3-1 cells treated with activin A, SBE1 preferentially recruits Smad3, but not Smad2, and mediates Smad3-dependent activation of follistatin transcription. shRNA knockdown of end...Continue Reading

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Citations

Oct 9, 2013·Molecular and Cellular Endocrinology·Varykina G Thackray
Dec 25, 2008·The Journal of Biological Chemistry·Amy L BlountLouise M Bilezikjian
Apr 10, 2013·Molecular and Cellular Endocrinology·Kirsten J McTavishShunichi Shimasaki
Feb 15, 2012·Molecular and Cellular Endocrinology·Louise M BilezikjianWylie W Vale
Feb 18, 2009·Animal Genetics·K GieseckeO Distl
Oct 23, 2009·Reproduction in Domestic Animals = Zuchthygiene·K GieseckeO Distl
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Feb 9, 2018·Reproductive Biology and Endocrinology : RB&E·Michal ElbazEran Gershon
May 6, 2015·Molecular Endocrinology·Jérôme FortinDaniel J Bernard
Mar 1, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Holly A LeddyWolfgang Liedtke
May 8, 2013·The Journal of Biological Chemistry·Masayo Sakaki-YumotoRik Derynck

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