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Gene-specific transcription activation via long-range allosteric shape-shifting
Chung-Jung Tsai1, Ruth Nussinov
1Basic Science Program, SAIC-Frederick, Center for Cancer Research Nanobiology Program NCI-Frederick, Frederick, MD 21702, USA.
The Biochemical Journal
|September 16, 2011
Summary
Regulatory elements transmit gene activation signals over long distances via transcription factors and the Mediator complex. This occurs through allosteric pathways, altering Mediator conformation to control transcription initiation and specificity.
Area of Science:
- Molecular Biology
- Gene Regulation
- Biochemistry
Background:
- Regulatory elements (REs) are often distant from transcription start sites.
- Understanding how REs influence transcription initiation over long distances is crucial.
Purpose of the Study:
- To review mechanisms of signal transmission from REs to the basal transcription machinery.
- To propose allosteric pathways involving transcription factors (TFs) and the Mediator complex.
Main Methods:
- Literature review of Mediator composition, structure, and interactions.
- Analysis of TF-RE binding and its effect on Mediator conformation.
- Hypothesizing allosteric signal propagation pathways.
Main Results:
- Mediator complex, composed of disordered proteins, facilitates long-range signal propagation.
- Two proposed mechanisms for Mediator action: influencing pre-initiation complex (PIC) assembly or acting on stalled transcription complexes.
- Allosteric signaling from REs to transcription activation provides mechanistic insight.
Conclusions:
- Allosteric pathways involving TFs and Mediator mediate gene specificity and signal transmission.
- Mediator conformation changes are central to regulating transcription initiation.
- This model offers a mechanistic view of how REs control transcription.
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