Specification of unique Pit-1 activity in the hGH locus control region.
The human GH (hGH) gene cluster is regulated by a remote 5' locus control region ( LCR). HSI, an LCR component located 14.5 kb 5' to the hGH-N promoter, constitutes the primary determinant of high-level hGH-N activation in pituitary somatotropes. HSI encompasses an array of three binding sites for the pituitary-specific POU homeodomain factor Pit-1. In the present report we demonstrate that all three Pit-1 sites in the HSI array contribute to LCR activity in vivo. Furthermore, these three sites as a unit are fully sufficient for position-independent and somatotrope-restricted hGH-N transgene activation. In contrast, the hGH-N transgene is not activated by Pit-1 sites native to either the hGH-N or rat (r)GH gene promoters. These findings suggest that the structures of the Pit-1 binding sites at HSI specify distinct chromatin-dependent activities essential for LCR- mediated activation of hGH in the developing pituitary.[1]References
- Specification of unique Pit-1 activity in the hGH locus control region. Shewchuk, B.M., Liebhaber, S.A., Cooke, N.E. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
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