The Pit-1 gene is regulated by distinct early and late pituitary-specific enhancers.
The differentiation of three anterior pituitary cell types is regulated by the tissue-specific POU domain factor Pit-1, which is initially expressed on Embryonic Day 13.5-14 in mice. The Pit-1 gene remains continuously, highly expressed in the somatotrope, thyrotrope, and lactotrope cells of the adult. Using the Pit-1-defective Snell dwarf as a genetic background, we demonstrate that the Pit-1 gene utilizes distinct enhancers for initial gene activation and for subsequent autoregulation (required for maintenance of expression) and that Pit-1-dependent activation of the distal enhancer can be mediated in the absence of the early enhancer. These two distinct enhancers provide the basis for temporally specific regulation by discrete pituitary-specific factors, events likely to be prototypic for regulation of other classes of genes encoding transcription factors controlling terminal differentiation.
DiMattia
G E
GE
Howard Hughes Medical Institute, Department and School of Medicine, University of California at San Diego, La Jolla 92093-0648, USA.
Rhodes
S J
SJ
Krones
A
A
Carrière
C
C
O'Connell
S
S
Kalla
K
K
Arias
C
C
Sawchenko
P
P
Rosenfeld
M G
MG
D000818:Animals; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004392:Dwarfism / Q000235:genetics; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000096:biosynthesis; D019382:Human Growth Hormone / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009928:Organ Specificity; D010903:Pituitary Gland, Anterior / Q000196:embryology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000096:biosynthesis*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D019382:Human Growth Hormone; D011993:Recombinant Fusion Proteins; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; C494187:POU1F1 protein, human; C494185:Pou1f1 protein, mouse