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Science 10 November 2000:
Vol. 290. no. 5494, pp. 1127 - 1131
DOI: 10.1126/science.290.5494.1127
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Research Articles

Allosteric Effects of Pit-1 DNA Sites on Long-Term Repression in Cell Type Specification

Kathleen M. Scully,1 Eric M. Jacobson,4 Kristen Jepsen,15 Victoria Lunyak,1 Hector Viadiu,4 Catherine Carrière,1 David W. Rose,2 Farideh Hooshmand,13 Aneel K. Aggarwal,4* Michael G. Rosenfeld1*

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.

1 Howard Hughes Medical Institute;
2 Department of Endocrinology and Metabolism;
3 Transgenic Research Unit; and Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
4 Structural Biology Program, Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, NY 10029, USA.
5 Department of Biology, University of California, San Diego, La Jolla, CA 92093, USA.
*   To whom correspondence should be addressed. E-mail: aggarwal{at}inka.mssm.edu (A.K.A.) and mrosenfeld{at}ucsd.edu (M.G.R.)

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Large-scale analysis of the human and mouse transcriptomes.
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Large-scale analysis of the human and mouse transcriptomes.
A. I. Su, M. P. Cooke, K. A. Ching, Y. Hakak, J. R. Walker, T. Wiltshire, A. P. Orth, R. G. Vega, L. M. Sapinoso, A. Moqrich, et al. (2002)
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