Paired-Like Homeodomain Transcription Factors 1 and 2 Regulate Follicle-Stimulating Hormone β-Subunit Transcription through a Conserved cis-Element

• DOI: 10.1210/en.2007-0425
• Publication Date: 2008-03-14T00:53:36Z
• Authors: Pankaj Lamba; Vishal Khivansara; Ana C. D'Alessio; Michelle M. Santos; Daniel J. Bernard
• Keywords: Response element; Transcription; General transcription factor; E-box

Paired-like homeodomain transcription factors (PITX) regulate the activity of pituitary hormone-encoding genes. Here, we examined mechanisms through which family PITX proteins control murine FSH β-subunit (Fshb) transcription. We observed that endogenous PITX1 and PITX2 isoforms from LβT2 gonadotrope cells could bind a highly conserved proximal cis-element. Transfection or PITX2C in heterologous stimulated both human Fshb/FSHB promoter-reporter activities, cases, mutation critical cis-element abrogated these effects. In homologous cells, same decreased basal reporter greatly reduced activin A-stimulated promoter-reporters. Transfecting dominant-negative forms knocking down -2 expression by RNA interference inhibited Fshb transcription, confirming roles for proteins. Both interacted with Smad3 (an effector signaling cascade cells) coprecipitation experiments, binding site Smad2/3/4-stimulated summary, promoter. Furthermore, data indicate common distinct action.