Figure 10. The haemoglobin analogy in gene regulation.

(A) The two conformations of haemoglobin are each adapted to one of the two input-output functions which haemoglobin integrates to solve the oxygen transport problem. These conformations dynamically interchange in the ensemble (grey dashed arrows). (B) The gene regulatory machinery couples input patterns of transcription factors (TFs) (left) to output patterns of stochastic expression of mRNA splice isoforms (right, showing bursting patterns of one isoform). Our results suggest that a sufficiently complex conformational ensemble, built out of chromatin, TFs, co-regulators and phase-separated condensates (centre, grey shapes in three distinct conformations), could integrate these functions at a single gene in an analogous way to haemoglobin. Chromatin is represented by the thick black curve, whose looped arrangement around the promoter is shown schematically (top).