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Open Access Highly Accessed Commentary

To bind or not to bind – how to down-regulate target genes by liganded thyroid hormone receptor?

Joachim M Weitzel

Author Affiliations

Institute of Experimental Endocrinology, Charité University Medicine Berlin, 13353 Berlin, Germany

Department of Reproductive Biology, FBN Dummerstorf, 18196 Dummerstorf, Germany

Thyroid Research 2008, 1:4  doi:10.1186/1756-6614-1-4

Published: 11 October 2008


The terrain is well explored regarding genes whose gene expression is up-regulated upon binding of thyroid hormone (TH) to its nuclear receptor. This regulation mechanism has been intensively studied and is well understood. In contrast, a lot of white spots remain on the map when it comes to target genes whose expression is down-regulated upon binding of TH to the thyroid hormone receptor (TR). Since no consistent mechanism has been proposed to explain ligand-dependent down-regulation of target gene transcription several working hypotheses favour different molecular mechanisms. Some working theories suggest a direct binding of TR to regulatory elements of target genes. Others favour models that are independent of a direct DNA binding event. However recent data suggested that a direct binding of TR to DNA is dispensable for TH-dependent negative gene transcription.