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Publication : Allosteric effects of Pit-1 DNA sites on long-term repression in cell type specification.

First Author  Scully KM Year  2000
Journal  Science Volume  290
Issue  5494 Pages  1127-31
PubMed ID  11073444 Mgi Jnum  J:65820
Mgi Id  MGI:1927333 Doi  10.1126/science.290.5494.1127
Citation  Scully KM, et al. (2000) Allosteric effects of pit-1 DNA sites on long-term repression in cell type specification. Science 290(5494):1127-31
abstractText  Reciprocal gene activation and restriction during cell type differentiation from a common lineage is a hallmark of mammalian organogenesis. A key question, then, is whether a critical transcriptional activator of cell type-specific gene targets can also restrict expression of the same genes in other cell types. Here, we show that whereas the pituitary-specific POU domain factor Pit-1 activates growth hormone gene expression in one cell type, the somatotrope, it restricts its expression from a second cell type, the lactotrope. This distinction depends on a two-base pair spacing in accommodation of the bipartite POU domains on a conserved growth hormone promoter site. The allosteric effect on Pit-1, in combination with other DNA binding factors, results in the recruitment of a corepressor complex, including nuclear receptor corepressor N-CoR, which, unexpectedly, is required for active long-term repression of the growth hormone gene in lactotropes.
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