Architectural proteins: regulators of 3D genome organization in cell fate

•The eukaryotic genome is organized into highly interactive domains called TADs.•Architectural proteins control TAD border strength to regulate inter- and intra-TAD interactions.•Architectural proteins control different steps of the transcription process.•The effects of architectural proteins on transcription determine cell differentiation outcomes.

The relation between alterations in chromatin structure and changes in gene expression during cell differentiation has served as a paradigm to understand the link between genome organization and function. Yet, the factors involved and the mechanisms by which the 3D organization of the nucleus is established remain poorly understood. The use of Chromosome Conformation-Capture (3C)-based approaches has resulted in a new appreciation of the role of architectural proteins in the establishment of 3D genome organization. Architectural proteins orchestrate higher-order chromatin organization through the establishment of interactions between regulatory elements across multiple spatial scales. The regulation of these proteins, their interaction with DNA, and their co-occurrence in the genome, may be responsible for the plasticity of 3D chromatin architecture that dictates cell and time-specific blueprints of gene expression.