title: A pituitary-specific enhancer of the POMC gene with preferential activity in corticotrope cells.
abstract: Cell-specific expression of the pituitary proopiomelanocortin (POMC) gene depends on the combination of tissue- and cell-restricted transcription factors such as Pitx1 and Tpit. These factors act on the proximal POMC promoter together with transcription factors that integrate inputs from signaling pathways. We now report the identification of an upstream enhancer in the POMC locus that is targeted by the same subset of transcription factors, except Pitx1. This enhancer located at -7 kb in the mouse POMC gene is highly dependent on Tpit for activity. Whereas Tpit requires Pitx1 for action on the promoter, it acts on the -7-kb enhancer as homodimers binding to a palindromic Tpit response element (TpitRE). Both half-sites of the TpitRE palindrome and Tpit homodimerization are required for activity. In vivo, the enhancer exhibits preferential activity in corticotrope cells of the anterior lobe whereas the promoter exhibits preference for intermediate lobe melanotropes. The enhancer is conserved among different species with the TpitRE palindrome localized at the center of conserved sequences. However, the mouse and human -7-kb enhancers do not exhibit conservation of hormone responsiveness and may differ in their relative importance for POMC expression. In summary, pituitary expression of the POMC gene relies on an upstream enhancer that complements the activity of the proximal promoter with Tpit as the major regulator of both regulatory regions.
authors.affiliation: Institut de recherches cliniques de Montréal, Montréal, QC, H2W 1R7, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Langlais
authors.forename: Catherine
authors.initials: C
authors.lastname: Couture
authors.forename: Guillaume
authors.initials: G
authors.lastname: Sylvain-Drolet
authors.forename: Jacques
authors.initials: J
authors.lastname: Drouin
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D052680:Corticotrophs / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D052717:Melanotrophs / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D010902:Pituitary Gland / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011333:Pro-Opiomelanocortin / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D020218:Response Elements; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; D051761:Paired Box Transcription Factors; D020825:T-Box Domain Proteins; C424031:Tbx19 protein, mouse; C101485:homeobox protein PITX1; D011333:Pro-Opiomelanocortin