Dynamics of nuclear receptor movement and transcription.

Following a hormone signal, steroid/nuclear receptors bind regulatory elements in chromatin and initiate the recruitment of a variety of multi-protein complexes to promoter sequences. These complexes ultimately lead to the recruitment of general transcription factors and the initiation of transcription. Traditional models suggest that these factors remain statically bound to each other and to chromatin until other signals are received to reduce transcription. Recent findings demonstrate that the processes and actions involved are much more complex than traditional models convey, and that the movement of receptors and coactivators is remarkably dynamic. Transcription factors are highly mobile in the nuclear environment, and interact only briefly with target sites in the nucleus. As a result of these transient interactions, promoters move through many states during activation and repression. Two general concepts emerge from current data: (1) Various transcription factors appear to follow "ordered recruitment" to promoters on a time scale of minutes to hours in response to a stimulus. During this response, the proteins that interact with chromatin may cycle on and off the promoter multiple times. (2) During these ordered recruitment cycles, the individual molecules that form functional complexes often exchange rapidly on a time scale of seconds. This rapid exchange of molecules within a formed complex occurs independently of long-term cycling on chromatin. Several processes are implicated in rapid nuclear dynamics, including potential roles for molecular chaperones, the proteasome degradation machinery and chromatin remodeling complexes.