Figure 1

Equilibrium and non-equilibrium events in gene regulation. (A) Thermodynamic equilibrium depiction of transcriptional regulation in prokaryotes. A transcription factor (blue) reversibly binds to naked DNA with a given affinity driven by mass action. The bound transcription factor then reversibly recruits RNA polymerase (red) to initiate transcription. (B) Examples of non-equilibrium processes involved in eukaryotic gene regulation. On the left, ATP-dependent nucleosome remodeling is shown. On the right, transcription factor phosphorylation is depicted. Such energy-dissipating processes are known to be involved in eukaryotic transcription, though these events are frequently left out of mathematical and computational models of gene regulation. (C) Cartoon of a dramatically over-simplified mammalian transcription initiation complex. Nucleosome remodeling and modification, transcription factor clustering in a ‘super-enhancer’, DNA looping, transcription factor and RNA-polymerase phosphorylation and cooperative binding interactions between general transcription factors, mediator, a distal enhancer and RNA polymerase all occur in these dynamic structures that are very far from equilibrium.