Other steps include recruitment of chromatin remodeling factors and cofactors that increase or decrease the rates of transcription –. The initially formed, intracellular receptor-steroid complex binds to specific enhancer-like DNA elements (called hormone response elements, or HREs) to eventually modify the rates of transcription of target genes. Steroid-regulated gene induction is an extensively studied paradigm with numerous well-defined events. Ligand-regulated gene induction is a productive experimental system for examining the mechanisms of gene expression. Thus new tools to determine previously unobtainable information about the nature and position of cofactor action in any process displaying first-order Hill plot kinetics are now available.
The analysis of TIF2 and sSMRT actions on GR-induction of an endogenous gene gave results identical to those with an exogenous reporter. The predictions of the theory, which can be applied using graphical methods similar to those of enzyme kinetics, are validated by obtaining internally consistent data for pair-wise analyses of three cofactors (TIF2, sSMRT, and NCoR) in U2OS cells. Here we show that a new mathematical theory of steroid hormone action can be used to deduce the kinetic properties and reaction sequence position for the functioning of any two cofactors relative to a concentration limiting step (CLS) and to each other. Two critical questions are (1) the steps at which cofactors exert their biological activities and (2) the nature of that activity.
Cofactors are intimately involved in steroid-regulated gene expression.
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