Nature 377, 397 - 404 (05 October 2002); doi:10.1038/377397a0

Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor

Andreas J. Hörlein^*, Anders M. Näär^*†, Thorsten Heinzel^*, Joseph Torchia^*, Bernd Gloss^*, Riki Kurokawa^‡, Aimee Ryan^*, Yasutomi Kamei^*, Mats Söderström^‡, Christopher K. Glass^‡ & Michael G. Rosenfeld^*

^*Howard Hughes Medical Institute, ^‡Cellular and Molecular Medicine, ^†Graduate Program in Molecular Pathology, Department and School of Medicine, University of California, San Diego, La Jolla, California 92093-0648, USA

Thyroid-hormone and retinoic-acid receptors exert their regulatory functions by acting as both activators and repressers of gene expression. A nuclear receptor co-repressor (N-CoR) of relative molecular mass 270K has been identified which mediates ligand-independent inhibition of gene transcription by these receptors, suggesting that the molecular mechanisms of repression by thyroid-hormone and retinoic-acid receptors are analogous to the co-repressor-dependent transcriptional inhibitory mechanisms of yeast and Drosophila.

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