Recent evidence that TADs and chromatin loops are dynamic structures

Abstract

Mammalian genomes are folded into spatial domains, which regulate gene expression by modulating enhancer-promoter contacts. Here, we review recent studies on the structure and function of Topologically Associating Domains (TADs) and chromatin loops. We discuss how loop extrusion models can explain TAD formation and evidence that TADs are formed by the ring-shaped protein complex, cohesin, and that TAD boundaries are established by the DNA-binding protein, CTCF. We discuss our recent genomic, biochemical and single-molecule imaging studies on CTCF and cohesin, which suggest that TADs and chromatin loops are dynamic structures. We highlight complementary polymer simulation studies and Hi-C studies employing acute depletion of CTCF and cohesin, which also support such a dynamic model. We discuss the limitations of each approach and conclude that in aggregate the available evidence argues against stable loops and supports a model where TADs are dynamic structures that continually form and break throughout the cell cycle.

Cited by papers we hold 5

• Cohesin and CTCF control the dynamics of chromosome folding · 2022
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• Wheat chromatin architecture is organized in genome territories and transcription factories · 2020
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• CTCF mediates chromatin looping via N-terminal domain-dependent cohesin retention · 2020
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• Determining cellular CTCF and cohesin abundances to constrain 3D genome models · 2019
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• Emerging Evidence of Chromosome Folding by Loop Extrusion · 2017
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