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Publication : Retinoic X receptor subtypes exert differential effects on the regulation of Trh transcription.

First Author  Decherf S Year  2013
Journal  Mol Cell Endocrinol Volume  381
Issue  1-2 Pages  115-23
PubMed ID  23896434 Mgi Jnum  J:211384
Mgi Id  MGI:5574570 Doi  10.1016/j.mce.2013.07.016
Citation  Decherf S, et al. (2013) Retinoic X receptor subtypes exert differential effects on the regulation of Trh transcription. Mol Cell Endocrinol 381(1-2):115-23
abstractText  How Retinoid X receptors (RXR) and thyroid hormone receptors (TR) interact on negative TREs and whether RXR subtype specificity is determinant in such regulations is unknown. In a set of functional studies, we analyzed RXR subtype effects in T3-dependent repression of hypothalamic thyrotropin-releasing hormone (Trh). Two-hybrid screening of a hypothalamic paraventricular nucleus cDNA bank revealed specific, T3-dependent interaction of TRs with RXRbeta. In vivo chromatin immuno-precipitation showed recruitment of RXRs to the TRE-site 4 region of the Trh promoter in the absence of T3. In vivo overexpression of RXRalpha in the mouse hypothalamus heightened T3-independent Trh transcription, whereas RXRbeta overexpression abrogated this activity. Loss of function of RXRalpha and beta by shRNAs induced inverse regulations. Thus, RXRalpha and RXRbeta display specific roles in modulating T3-dependent regulation of Trh. These results provide insight into the actions of these different TR heterodimerization partners within the context of a negatively regulated gene.
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