Epigenetic regulatory layers in the 3D nucleus

Nearly 7 decades have elapsed since Francis Crick introduced the central dogma of molecular biology, as part of his ideas on protein synthesis, setting the fundamental rules of sequence information transfer from DNA to RNAs and proteins. We have since learned that gene expression is finely tuned in time and space, due to the activities of RNAs and proteins on regulatory DNA elements, and through cell-type-specific three-dimensional conformations of the genome. Here, we review major advances in genome biology and discuss a set of ideas on gene regulation and highlight how various biomolecular assemblies lead to the formation of structural and regulatory features within the nucleus, with roles in transcriptional control. We conclude by suggesting further developments that will help capture the complex, dynamic, and often spatially restricted events that govern gene expression in mammalian cells. Genomes are folded into three-dimensional structures that serve as substrates for the actions of proteins and RNAs in gene regulation. Here, we give an overview of the many gene regulatory mechanisms that co-exist in living cells and elaborate on future approaches to deepen our understanding of their interplay in genome function.