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

K. H. Scully, E. M. Jacobson, K. Jepsen, V. Lunyak, H. Viadiu, C. Carriere, D. W. Rose, F. Hooshmand, A. K. Aggarwal, M. G. Rosenfeld

Research output: Contribution to journalReview articlepeer-review

217 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1127-1131
Number of pages5
JournalScience
Volume290
Issue number5494
DOIs
StatePublished - 10 Nov 2000

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