To bind or not to bind - how to down-regulate target genes by liganded thyroid hormone receptor?
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.
Weitzel
Joachim M
JM
Institute of Experimental Endocrinology, Charité University Medicine Berlin, 13353 Berlin, Germany. weitzel@fbn-dummerstorf.de.