Purkinje cell protein-2 cis-elements mediate repression of T3-dependent transcriptional activation

Grant W. Anderson, Steven G. Hagen, Ruby J. Larson, Kevin A. Strait, Harold L. Schwartz, Cary N. Mariash, Jack H. Oppenheimer

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Previous studies in our laboratory show that triiodothyronine upregulates expression of the cerebellar Purkinje cell-specific gene Pcp-2 during the first 2 weeks of rat neonatal life. A specific thyroid hormone response element, the A1 TRE, mediates this regulation. The finding that the contiguous 68 bases (-267/-199) of the Pcp-2 promoter 3' to the A1 TRE repressed T3 response in transactivation studies suggested that this sequence could play a role in preventing premature T3-dependent activation of Pcp-2 in the fetus. We now show that deletion of this region resulted in enhanced T3-dependent activation of the native Pcp-2 promoter. The sequence is not a generalized silencer since it does not alter basal activity of mouse mammary tumor virus (MMTV) or thymidine kinase (TK) promoters. Deletion and linker scanning studies indicate that the 5' 30 bases of the -267/-199 region mediate most of the response silencing activity. The -267/-199 region also attenuates T3-induced transactivation mediated by other TREs. Gel shift analysis reveals that nuclear proteins from fetal but not adult brains complex with the -267/-199 region, supporting the hypothesis that this region binds proteins that suppress Pcp-2 expression early in brain development.

Original languageEnglish (US)
Pages (from-to)79-87
Number of pages9
JournalMolecular and Cellular Endocrinology
Volume131
Issue number1
DOIs
StatePublished - Jul 4 1997

Bibliographical note

Funding Information:
We would like to express appreciation to Derek Blom for excellent technical assistance and Maria Purvey and Heather Turngren for editorial support. This work was supported by National Institutes of Health Grants AM 19812 (JHO), DK09295 (GWA) and DK08901 (SGH).

Keywords

  • Brain
  • Development
  • Thyroid hormone

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