This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jiang, S.-W. Articles by Eberhardt, N. L. Search for Related Content PubMed PubMed Citation Articles by Jiang, S.-W. Articles by Eberhardt, N. L.

The Human Chorionic Somatomammotropin Enhancers Form a Composite Silencer in Pituitary Cells in Vitro

Endocrine Research Unit Departments of Medicine and Biochemistry/Molecular Biology Mayo Clinic, Rochester, Minnesota 55905

The human GH (GH) gene family includes the pituitary-specific hGH-1, placental-specific chorionic somatomammotropin (hCS-5, hCS-2, and hCS-1), and hGH-2 genes. These duplicated, nearly identical genes are localized on approximately 50 kb of DNA on chromosome 17q₂₃-q₂₄. An enhancer (CSEn2), located downstream of the hCS-2 gene, participates in mediating placental-specific hCS gene expression. In the preceding paper we demonstrated that CSEn2 activity derives from the cooperative binding of transcription factor-1, TEF-1, and a placental-specific factor CSEF-1 to multiple enhansons, Enh1-Enh5, that are related to the SV40 GT-IIC and SphI/SphII enhansons. Here we demonstrate that two copies of CSEn2 or a single copy of CSEn2 linked to either of the other two enhancers in the hGH/hCS locus, CSEn1 and CSEn5, act cooperatively to enhance hCS promoter activity in choriocarcinoma (BeWo) cells, but silence the promoter in pituitary GC cells. Mutation of Enh4, an essential GT-IIC-like enhanson in the context of the intact enhancer, abolishes silencer activity, and multimerized GT-IIC enhansons mimic the intact CSEn enhancer/silencer activities in BeWo and GC cells, respectively. By antibody-mediated supershift, Western, and far Western analyses, we identified TEF-1 as the GT-IIC-binding factor in pituitary cells. The data suggest that TEF-1 may be involved in pituitary-specific repression of placental GH/CS gene transcription through long-range interactions between the multiple CS enhancers present on the GH/CS gene locus.

This article has been cited by other articles:

				F. Elefant, N. E. Cooke, and S. A. Liebhaber Targeted Recruitment of Histone Acetyltransferase Activity to a Locus Control Region J. Biol. Chem., April 28, 2000; 275(18): 13827 - 13834. [Abstract] [Full Text] [PDF]

				S.-W. Jiang, K. Wu, and N. L. Eberhardt Human Placental TEF-5 Transactivates the Human Chorionic Somatomammotropin Gene Enhancer Mol. Endocrinol., June 1, 1999; 13(6): 879 - 889. [Abstract] [Full Text]

				S.-W. Jiang, M. A. Trujillo, and N. L. Eberhardt Human Chorionic Somatomammotropin Enhancer Function Is Mediated by Cooperative Binding of TEF-1 and CSEF-1 to Multiple, Low-Affinity Binding Sites Mol. Endocrinol., August 1, 1997; 11(9): 1223 - 1232. [Abstract] [Full Text]