Crumpled Polymer with Loops Recapitulates Key Features of Chromosome Organization

Physical Review X, Journal Year: 2023, Volume and Issue: 13(4)

Published: Nov. 13, 2023

Chromosomes are exceedingly long topologically-constrained polymers compacted in a cell nucleus. We recently suggested that chromosomes organized into loops by an active process of loop extrusion. Yet remain elusive to direct observations living cells; detection and characterization myriads such is major challenge. The lack tractable physical model polymer folded limits our ability interpret experimental data detect loops. Here, we introduce new - sequence loops, solve it analytically. Our simple geometrical argument show how affect statistics contacts across different scales, explaining universally observed shapes the contact probability. Moreover, reveal folding reduces density topological entanglements, novel phenomenon refer as "the dilution entanglements". Supported simulations this finding suggests up ~ 1 2Mb with not topologically constrained, yet become crumpled at larger scales. theoretical framework allows inference characteristics, draws picture chromosome organization, shows affects properties polymers.

Language: Английский

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The role of loop extrusion in enhancer-mediated gene activation

Current Opinion in Genetics & Development, Journal Year: 2023, Volume and Issue: 79, P. 102022 - 102022

Published: Feb. 25, 2023

Gene expression patterns in complex multicellular organisms are regulated by enhancers, which communicate with their target gene promoters three-dimensional (3D) chromatin structures. Despite advances our understanding of the mechanisms that organize mammalian genomes into compartments and topologically associating domains (TADs), it is not well understood how specific interactions between enhancers controlled this 3D context. In review, we give an overview recent evidence shows a process loop extrusion plays important role regulation enhancer-promoter communication discuss insights molecular mechanism contributes to enhancer-mediated activation.

Language: Английский

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Synthetic analysis of chromatin tracing and live-cell imaging indicates pervasive spatial coupling between genes

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Feb. 14, 2023

The role of the spatial organization chromosomes in directing transcription remains an outstanding question gene regulation. Here, we analyze two recent single-cell imaging methodologies applied across hundreds genes to systematically contribution chromosome conformation transcriptional Those are (1) chromatin tracing with super-resolution fixed cells; and (2) high-throughput labeling nascent RNA living cells. Specifically, determine physical distance coordination bursts. We find that individual adopt a constrained reposition toward centroid surrounding upon activation. Leveraging variability inherent imaging, show - but not genomic between on is major factor driving co-bursting. By combining this analysis live-cell arrive at corrected correlation [Formula: see text] for separated by < 400 nm. propose surprisingly large represents property human establishes benchmark future experimental studies.

Language: Английский

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Ultra-long-range interactions between active regulatory elements

Genome Research, Journal Year: 2023, Volume and Issue: 33(8), P. 1269 - 1283

Published: July 14, 2023

Contacts between enhancers and promoters are thought to relate their ability activate transcription. Investigating factors that contribute such chromatin interactions is therefore important for understanding gene regulation. Here, we have determined contact frequencies millions of pairs

Language: Английский

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Linking chromatin acylation mark-defined proteome and genome in living cells

Cell, Journal Year: 2023, Volume and Issue: 186(5), P. 1066 - 1085.e36

Published: March 1, 2023

Language: Английский

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