Salari, H. | Search bioRxiv

bioRxiv2022

Context-dependent transcriptional remodeling of TADs during differentiation

Metazoan chromosomes are organized into discrete domains (TADs), believed to contribute to the regulation of transcriptional programs. Despite extensive correlation between TAD organization and gene activity, a direct mechanistic link is unclear, with perturbation studies often showing little effect. To follow TAD dynamics during development, we used Capture Hi-C to interrogate the TADs around key differentially expressed genes during mouse thymocyte maturation, uncovering specific remodeling events. Notably, one TAD boundary was broadened to accommodate RNA polymerase elongation past the border, and sub-domains were formed around some activated genes without changes in CTCF binding. The ectopic induction of one gene was sufficient to recapitulate microdomain formation in embryonic stem cells, providing strong evidence that transcription can directly remodel chromatin structure. These results suggest that transcriptional processes drive complex, but non-universal, chromosome folding patterns that can be important in certain genomic contexts.

genomics↗

bioRxiv2021

Spatial organization of chromosomes leads to heterogeneous chromatin motion and drives the liquid- or gel-like behavior of chromatin

Chromosome organization and dynamics are involved in regulating many fundamental processes such as gene transcription and DNA repair. Experiments unveiled that chromatin motion is highly heterogeneous inside cell nuclei, ranging from a liquid-like, mobile state to a gel-like, rigid regime. Using polymer modeling, we investigate how these different physical states and dynamical heterogeneities may emerge from the same structural mechanisms. We found that the formation of topologically-associating domains (TADs) is a key driver of chromatin motion heterogeneity. In particular, we demonstrated that the local degree of compaction of the TAD regulates the transition from a weakly compact, fluid state of chromatin to a more compact, gel state exhibiting anomalous diffusion and coherent motion. Our work provides a comprehensive study of chromosome dynamics and a unified view of chromatin motion enabling to interpret the wide variety of dynamical behaviors observed experimentally across different biological conditions, suggesting that the liquid or solid behaviour of chromatin are in fact two sides of the same coin.

biophysics↗