Reciprocal interactions of Pit1 and GATA2 mediate signaling gradient-induced determination of pituitary cell types

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Item Type:	Article
Title:	Reciprocal interactions of Pit1 and GATA2 mediate signaling gradient-induced determination of pituitary cell types
Creators Name:	Dasen, J.S., O'Connell, S.M., Flynn, S.E., Treier, M., Gleiberman, A.S., Szeto, D.P., Hooshmand, F., Aggarwal, A.K. and Rosenfeld, M.G.
Abstract:	The mechanisms by which transient gradients of signaling molecules lead to emergence of specific cell types remain a central question in mammalian organogenesis. Here, we demonstrate that the appearance of four ventral pituitary cell types is mediated via the reciprocal interactions of two transcription factors, Pit1 and GATA2, which are epistatic to the remainder of the cell type–specific transcription programs and serve as the molecular memory of the transient signaling events. Unexpectedly, this program includes a DNA binding–independent function of Pit1, suppressing the ventral GATA2-dependent gonadotrope program by inhibiting GATA2 binding to gonadotrope- but not thyrotrope-specific genes, indicating that both DNA binding–dependent and –independent actions of abundant determining factors contribute to generate distinct cell phenotypes.
Keywords:	Amino Acid Sequence, Amino Acid Substitution, Base Sequence, COS Cells, DNA-Binding Proteins, GATA2 Transcription Factor, Genetic Promoter Regions, Genetic Transcription, Homeodomain Proteins, Molecular Sequence Data, Pituitary Gland, Point Mutation, Recombinant Proteins, Reporter Genes, Signal Transduction, Site-Directed Mutagenesis, Thyrotropin, Transcription Factor Pit-1, Transcription Factors, Transfection, Transgenic Mice, Zinc Fingers, Animals, Mice, Rats
Source:	Cell
ISSN:	0092-8674
Publisher:	Cell Press
Volume:	97
Number:	5
Page Range:	587-598
Date:	28 May 1999
Official Publication:	https://doi.org/10.1016/S0092-8674(00)80770-9
PubMed:	View item in PubMed

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