A composite element that binds basic helix loop helix and basic leucine zipper transcription factors is important for gonadotropin-releasing hormone regulation of the follicle-stimulating hormone β gene

Nick A. Ciccone, Charlemagne T. Lacza, Melody Hou, Susan J. Gregory, Kyung Yoon Kam, Shuyun Xu, Ursula B. Kaiser

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Although FSH plays an essential role in controlling gametogenesis, the biology of FSHβ transcription remains poorly understood, but is known to involve the complex interplay of multiple endocrine factors including GnRH. We have identified a GnRH-responsive element within the rat FSHβ promoter containing an E-box and partial cAMP response element site that are bound by the basic helix loop helix transcription factor family members, upstream stimulating factor (USF)-1/USF-2, and the basic leucine zipper member, cAMP response element-binding protein (CREB), respectively. Expression studies with CREB, USF-1/USF-2, and activating protein-1 demonstrated that the USF transcription factors increased basal transcription, an effect not observed if the cognate binding site was mutated. Conversely, expression of a dominant negative CREB mutant or CREB knockdown attenuated induction by GnRH, whereas dominant negative Fos or USF had no effect on the GnRH response. GnRH stimulation specifically induced an increase in phosphorylated CREB occupation of the FSHβ promoter, leading to the recruitment of CREB-binding protein to enhance gene transcription. In conclusion, a composite element bound by both USF and CREB serves to integrate signals for basal and GnRH-stimulated transcription of the rat FSHβ gene.

Original languageEnglish (US)
Pages (from-to)1908-1923
Number of pages16
JournalMolecular Endocrinology
Volume22
Issue number8
DOIs
StatePublished - Aug 2008
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Fingerprint Dive into the research topics of 'A composite element that binds basic helix loop helix and basic leucine zipper transcription factors is important for gonadotropin-releasing hormone regulation of the follicle-stimulating hormone β gene'. Together they form a unique fingerprint.

  • Cite this