Figure 2.

Three proposed mechanisms of TF selectivity. The classification is based on a conformational ensemble framework. (a) All REs are exposed and available for binding to TFs. The TF selectively binds an RE whose conformation is complementary (here in green). The TF-binding site conformation is allosterically determined by the prior binding events (not shown) of factors whose concentrations are controlled by the cellular network. Once the TF binds to an RE, transcription is initiated (or repressed). (b) All REs are available and the TF can bind to any (or all) REs. The REs allosterically enhance a TF population favored to bind to a specific cofactor. Each RE elicits a slightly different conformation of the binding site (different shapes in the upper part of the TF). The cofactor binds to the binding site conformation, which is complementary. When the cofactor binds, transcription is initiated (or repressed). Here, selectivity is determined by post binding events. (c) Chromatin unavailable REs become exposed through the enhanceosome (e.g. acetylation).