The Mediator Complex: Progress over the Past Decade

The Mediator complex is a central regulator of eukaryotic transcription, functioning as a dynamic molecular bridge between gene-specific transcription factors and RNA polymerase II (Pol II). Although decades of research have established its modular architecture and fundamental role in transcriptional control, recent advances have significantly expanded our understanding of its structural conformations, subunit-specific functions, and links to human disease. This review provides a comprehensive overview of the Mediator complex, highlighting key structural and functional discoveries from the past decade and synthesizing its diverse roles in transcriptional regulation. We further discuss emerging concepts and future directions for therapeutically targeting Mediator, particularly in cancer. Together, these insights position the Mediator complex as a highly conserved yet adaptable, signal-responsive regulatory hub with broad implications for both normal physiology and disease pathogenesis.