Differential regulation of the human progesterone receptor gene through an estrogen response element half site and Sp1 sites

Larry N. Petz, Yvonne S. Ziegler, Jennifer R. Schultz, Hwajin Kim, J. Kim Kemper, Ann M. Nardulli

Research output: Contribution to journalArticlepeer-review

Abstract

The progesterone receptor (PR) gene is regulated by estrogen in normal reproductive tissues and in MCF-7 human breast cancer cells. Although it is generally thought that estrogen responsiveness is mediated by interaction of the ligand-occupied estrogen receptor (ER) with estrogen response elements (EREs) in target genes, the human progesterone receptor (PR) gene lacks a palindromic ERE. Promoter A of the PR gene does, however, contain an ERE half site upstream of two adjacent Sp1 sites from +571 to +595, the +571 ERE/Sp1 site. We have examined the individual contributions of the ERE half site and the two Sp1 sites in regulating estrogen responsiveness. Transient transfection assays demonstrated that both Sp1 sites were critical for estrogen-mediated activation of the PR gene. Interestingly, rather than decreasing transcription, mutations in the ERE half site increased transcription substantially suggesting that this site plays a role in limiting transcription. Chromatin immunoprecipitation assays demonstrated that Sp1 was associated with the +571 ERE/Sp1 site in the endogenous PR gene in the absence and in the presence of estrogen, but that ERα was only associated with this region of the PR gene after MCF-7 cells had been treated with estrogen. Our studies provide evidence that effective regulation of transcription through the +571 ERE/Sp1 site requires the binding of ERα and Sp1 to their respective cis elements and the appropriate interaction of ERα and Sp1 with other coregulatory proteins and transcription factors.

Original languageEnglish (US)
Pages (from-to)113-122
Number of pages10
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume88
Issue number2
DOIs
StatePublished - Feb 1 2004

Keywords

  • ERE
  • Estrogen receptor
  • Gene expression
  • Progesterone receptor
  • Sp1

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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