Estrogen receptor alpha and Sp1 regulate progesterone receptor gene expression.
The progesterone receptor (PR) gene is induced by estrogen in reproductive and mammary tissues and in MCF-7 human breast cancer cells even though the human PR gene lacks an estrogen response element. We have identified a region from -80 to -34 in the PR gene that contains two Sp1 sites and confers estrogen responsiveness to a heterologous promoter in an estrogen and estrogen receptoralpha (ERalpha)-dependent manner. Sp1 present in MCF-7 nuclear extracts and purified Sp1 bind to and protect both Sp1 sites from DNase I cleavage, but the proximal Sp1 site is preferentially protected. Mutation of either Sp1 site decreases Sp1-DNA complex formation and ERalpha-mediated transactivation. ERalpha enhances Sp1 binding, but does not interact directly with the -80/-34 region. Our studies suggest that ERalpha confers estrogen responsiveness to the PR gene by enhancing Sp1 interaction with the Sp1 site in the -80/-34 region of the human PR gene.
Schultz
Jennifer R
JR
Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, 524 Burrill Hall, 407 South Goodwin Avenue, 61801, USA.
Petz
Larry N
LN
Nardulli
Ann M
AM
D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D018983:DNA Footprinting; D047628:Estrogen Receptor alpha; D004967:Estrogens / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D009154:Mutation; D011401:Promoter Regions, Genetic; D011960:Receptors, Estrogen / Q000502:physiology*; D011980:Receptors, Progesterone / Q000235:genetics* / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000502:physiology*; D016329:Sp1 Transcription Factor / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D047628:Estrogen Receptor alpha; D004967:Estrogens; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011988:Receptors, Thyroid Hormone; D016329:Sp1 Transcription Factor