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Related Experiment Videos

Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human

P Kastner1, A Krust, B Turcotte

  • 1Laboratoire de Génétique Moléculaire des Eucaryotes, CNRS, Strasbourg, France.

The EMBO Journal
|May 1, 1990
PubMed
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This study identifies two distinct promoters regulating human progesterone receptor (hPR) gene expression, leading to the production of hPR-A and hPR-B forms. Both promoters are estrogen-inducible and influence receptor activity differently.

Area of Science:

  • Molecular Biology
  • Endocrinology
  • Genetics

Background:

  • The human progesterone receptor (hPR) is a key nuclear receptor involved in various physiological processes.
  • Understanding the regulation of hPR gene expression is crucial for comprehending its role in health and disease, particularly in breast cancer.

Purpose of the Study:

  • To characterize the gene structure and regulatory elements of the human progesterone receptor.
  • To identify the mechanisms responsible for the differential expression of hPR-A and hPR-B isoforms.

Main Methods:

  • Cloning and sequencing of hPR cDNA and its 5'-flanking region.
  • Northern blot analysis and S1 nuclease mapping to analyze hPR mRNA transcripts.
  • Functional analysis of promoter activity using chimeric genes and transient co-transfection assays.

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Main Results:

  • Two distinct hPR mRNA classes were identified, encoding hPR-A and hPR-B forms, originating from different translational initiation sites.
  • Two functional promoters were identified in the hPR gene's 5'-flanking region, regulating transcription initiation.
  • Both promoters were found to be estrogen-inducible, independent of a classical estrogen-responsive element.
  • hPR-A and hPR-B exhibited differential transcriptional activation capabilities on various reporter gene constructs.

Conclusions:

  • The human progesterone receptor gene is regulated by at least two distinct, estrogen-inducible promoters.
  • Differential expression of hPR-A and hPR-B isoforms is achieved through distinct transcriptional initiation events.
  • The identified promoters and isoforms play specific roles in transcriptional regulation, offering insights into progesterone receptor function.