TADs: Dynamic structures to create stable regulatory functions

• Published in: Current opinion in structural biology Vol. 81; p. 102622
• Main Authors: da Costa-Nunes, José A., Noordermeer, Daan
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2023; Elsevier
• Subjects: Animals; Cell Nucleus; Chromatin; Chromosomes, Mammalian; Cohesin; CTCF; Enhancer-promoter looping; Gene Expression Regulation; Genome; Life Sciences; Loop extrusion; Mammals - genetics; TADs; Enhancer-promoter looping; TADs; Cohesin; CTCF; Loop extrusion; enhancer-promoter looping; loop extrusion
• ISSN: 0959-440X; 1879-033X
• DOI: 10.1016/j.sbi.2023.102622

Mammalian chromosomes are organized at different length scales within the cell nucleus. Topologically Associating Domains (TADs) are structural units of 3D genome organization with functions in gene regulation, DNA replication, recombination and repair. Whereas TADs were initially interpreted as insulated domains, recent studies are revealing that these domains should be interpreted as dynamic collections of actively extruding loops. This process of loop extrusion is subsequently blocked at dedicated TAD boundaries, thereby promoting intra-domain interactions over their surroundings. In this review, we discuss how mammalian TAD structure can emerge from this dynamic process and we discuss recent evidence that TAD boundaries can have regulatory functions. •TADs act as regulatory neighborhoods for genome-associated processes.•TADs are dynamic entities containing a relatively low-density of extruded loops.•TADs are actively involved in long intra-TAD enhancer-promoter loop formation.•TAD boundaries fine-tune loop extrusion via protein interactions and DNA sequence.