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A purkinje cell protein-2 intronic thyroid hormone response element binds developmentally regulated thyroid hormone receptor-nuclear protein complexes

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Abstract

Two thyroid hormone response elements (TREs), designated A1 TRE (−295/−268) and B1 TRE (+207/+227), have been identified within the Purkinje cell-expressed Pcp-2 gene. Previous studies have characterized the A1 TRE (Zou et al., 1994). This article analyzes the structural and functional characteristics of the intronic B1 TRE. The B1 sequence contains four overlapping TRE half-sites. The 3′ DR4 motif, consisting of the second and forth half-sites, is responsible for the T3 induction observed with the B1 sequence. Gel-shift analysis reveals developmentally regulated complexes that are abundant in the fetus and at birth and then fall precipitously in the neonate bind to B1. The observed time-course of these complexes varies inversely with the rise in Pcp-2 expression, thus raising the possibility that the complexes may represent inhibitory factors. Supershift analysis indicates that endogenous TRα1 is present in the fetal nuclear protein complexes that bind to B1. Competition analysis also indicates the second B1 TRE half-site is important in binding the TRα1-TRAP complexes. These studies suggest that the B1 sequence may bind potential TRα1-TRAP repressor complexes in the fetus, whereas in the neonate, these TRE sites may be involved in the activation of Pcp-2 by binding other TR-TRAP-activating complexes.

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Abbreviations

T3:

3,5,3′-l-triiodothyronine (thyroid hormone)

TR(s):

thyroid hormone receptor(s)

TRE(s):

thyroid hormone response element(s)

RXR:

9-cis retinoic acid receptor

Pcp-2:

Purkinje cell protein-2

DR4:

direct repeat 4

TRAP(s):

thyroid hormone receptor auxiliary protein(s)

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Authors and Affiliations

  1. Thyroid Research Unit, Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, University of Minnesota, 55455, Minneapolis, MN

    Steven G. Hagen, Ruby J. Larson, Kevin A. Strait & Jack H. Oppenheimer

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  1. Steven G. Hagen
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  2. Ruby J. Larson
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  3. Kevin A. Strait
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  4. Jack H. Oppenheimer
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Hagen, S.G., Larson, R.J., Strait, K.A. et al. A purkinje cell protein-2 intronic thyroid hormone response element binds developmentally regulated thyroid hormone receptor-nuclear protein complexes. J Mol Neurosci 7, 245–255 (1996). https://doi.org/10.1007/BF02737062

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  • DOI: https://doi.org/10.1007/BF02737062

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