From 3D organization of the genome to gene expression

The eukaryotic genome is hierarchically packaged inside the nucleus. DNA and proteins form the chromatin fibers that are organized in a complex three-dimensional (3D) structure, which includes multiscale structural units ranging from chromosome territories, compartments, topologically associating domains, and local condensations to the level of a single nucleosome. This complex 3D chromatin organization plays an essential role in transcription regulation and gene expression, which are crucial for the life of the organism. In this review, we describe basic principles of transcription regulation and higher-order chromatin organization that play a role in controlling the spatiotemporal expression of genes. We discuss the function of both coding and noncoding sequences, transcription factors, epigenetic modifications, chromatin looping and architecture in transcription regulation, and gene activation. Finally, we describe recent evidence for the role of phase separation in 3D chromatin organization and in the dynamics of transcription hubs at specific genomic loci that drive spatiotemporal gene expression.