Mutual remodeling and conformation grid: a mediator code?

Abstract

How does a common RNA polymerase II apparatus generate a complex pattern of transcripts in response to many gene-specific transcription factors and in accordance with cell's state? In this issue of Structure, Cai et al. reveal that the process involves coordinated conformational changes in Pol II and Mediator.

Fig. 1

Mutual remodeling of Pol II and the Mediator Head in the mPIC. (A) Architecture of unbound Pol II as found in its crystal structure. The relevant domains are marked. (B) Domain arrangement of unbound Head module in its crystal structure (PDB ID: 3RJ1). (C) The rearranged domains of Pol II and the Head module when they interact in the mPIC.

Fig. 2

A conformational grid for the Pol II holoenzyme. (A) Variations in both the subunit composition of Mediator (horizontal dimension) and the binding of transcription factor/cofactor (vertical) give rise to an array of discrete holoenzyme conformations, under a given cell state (State-1, green array). Pol II, red; Mediator, dark blue. The CDK8 module (yellow) is depicted following the S. pombe complex. (B) In the third dimension, a change in cell state leads to modifications of various transcription factors and cofactors, resulting in a different array of conformations (State-2, brown array). (C) Transcriptomes (represented as gene-chip patterns) of State-1 and State-2 are generated corresponding to the cell state-specific conformation arrays, the green and brown array in B, respectively.