To bind or not to bind – how to down-regulate target genes by liganded thyroid hormone receptor?
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:10.1186/1756-6614-1-4Published: 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.