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Published on: September 8, 2021
The Mediator complex: co-transcriptional regulation and beyond
Yenan Yang1,2, Yuanming Zheng2, Qiang Zhou1
1School of Biological Sciences, Faculty of Science, The University of Hong Kong, Hong Kong, China.
Abstract:
The Mediator complex functions as a central multi-subunit coactivator essential for RNA polymerase II-dependent transcription in eukaryotes, integrating signals from enhancers to promoters across the transcription cycle. This review summarizes its modular composition and structural dynamics revealed by cryo-EM, and details its mechanistic roles in pre-initiation complex assembly, promoter-proximal pausing release, elongation progression, co-transcriptional splicing, termination via 3'-end processing, and chromatin changes. Recent progress elucidates allosteric signal transmission, TF multivalency, cohesin-mediated looping, and phase separation, while dysregulation implicates Mediator in cancer and developmental disorders. Future directions emphasize in vivo kinetics and therapeutic targeting of kinase modules to decode context-specific gene control.
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