The co-chaperone XAP2 is required for activation of hypothalamic thyrotropin-releasing hormone transcription in vivo |
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| Authors: | Froidevaux Marie-Stéphanie Clerget Berg Petra Seugnet Isabelle Decherf Stéphanie Becker Nathalie Sachs Laurent M Bilesimo Patrice Nygård Maria Pongratz Ingemar Demeneix Barbara A |
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| Affiliation: | UMR 5166, CNRS/MNHN USM 501, 57 rue Cuvier, Bp 32, Paris Cedex 05, France. |
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| Abstract: | Transcriptional control of hypothalamic thyrotropin-releasing hormone (TRH) integrates central regulation of the hypothalamo-hypophyseal-thyroid axis and hence thyroid hormone (triiodothyronine (T(3))) homeostasis. The two beta thyroid hormone receptors, TRbeta1 and TRbeta2, contribute to T(3) feedback on TRH, with TRbeta1 having a more important role in the activation of TRH transcription. How TRbeta1 fulfils its role in activating TRH gene transcription is unknown. By using a yeast two-hybrid screening of a mouse hypothalamic complementary DNA library, we identified a novel partner for TRbeta1, hepatitis virus B X-associated protein 2 (XAP2), a protein first identified as a co-chaperone protein. TR-XAP2 interactions were TR isoform specific, being observed only with TRbeta1, and were enhanced by T(3) both in yeast and mammalian cells. Furthermore, small inhibitory RNA-mediated knockdown of XAP2 in vitro affected the stability of TRbeta1. In vivo, siXAP2 abrogated specifically TRbeta1-mediated (but not TRbeta2) activation of hypothalamic TRH transcription. This study provides the first in vivo demonstration of a regulatory, physiological role for XAP2. |
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