CHAPTER 13: Protein–DNA Interactions^†

In this chapter we describe how our understanding of molecular recognition in protein–DNA interactions at the level of stereochemistry and structural detail has been advanced by X-ray crystallography and nuclear magnetic resonance (NMR) and now further accelerated by cryogenic electron microscopy (cryo-EM) and machine learning. These approaches are moving to address challenging questions, such as, “How is the activity of transcription factors regulated?” “How does the organisation of chromatin into modular domains occur and how might that help to define programs of transcription?” With the development of powerful tools such as electron tomography and mapping transient interactions in situ by chromatin capture methods, we are moving toward the next stage of visualising higher order macromolecular organisation in situ, in both space and in time. These and other experimental and computational approaches will enable us to follow how the information encoded in the primary sequence of the hereditary material is manifested as the complex and difficult to predict readout, namely the biological phenotype upon which evolution acts blindly.