Nature, Journal Year: 2019, Volume and Issue: 568(7750), P. 49 - 54
Published: March 18, 2019
Language: Английский
Cell Reports, Journal Year: 2016, Volume and Issue: 15(9), P. 2038 - 2049
Published: May 1, 2016
Topologically associating domains (TADs) are fundamental structural and functional building blocks of human interphase chromosomes, yet the mechanisms TAD formation remain unclear. Here, we propose that loop extrusion underlies formation. In this process, cis-acting loop-extruding factors, likely cohesins, form progressively larger loops but stall at boundaries due to interactions with boundary proteins, including CTCF. Using polymer simulations, show model produces TADs finer-scale features Hi-C data. Each emerges from multiple dynamically formed through extrusion, contrary typical illustrations single static loops. Loop both explains diverse experimental observations—including preferential orientation CTCF motifs, enrichments architectural proteins boundaries, deletion experiments—and makes specific predictions for depletion versus cohesin. Finally, has potentially far-ranging consequences processes such as enhancer-promoter interactions, orientation-specific chromosomal looping, compaction mitotic chromosomes.
Language: Английский
Citations
1855
Nature Reviews Genetics, Journal Year: 2016, Volume and Issue: 17(11), P. 661 - 678
Published: Oct. 14, 2016
Language: Английский
Citations
1034
Nature Cell Biology, Journal Year: 2018, Volume and Issue: 21(1), P. 72 - 84
Published: Dec. 17, 2018
Language: Английский
Citations
1002
Cell, Journal Year: 2017, Volume and Issue: 171(1), P. 34 - 57
Published: Sept. 1, 2017
Language: Английский
Citations
986
Nature Reviews Genetics, Journal Year: 2019, Volume and Issue: 20(8), P. 437 - 455
Published: May 13, 2019
Language: Английский
Citations
946
Nature Reviews Molecular Cell Biology, Journal Year: 2017, Volume and Issue: 18(11), P. 685 - 701
Published: Sept. 6, 2017
Language: Английский
Citations
906
Science, Journal Year: 2018, Volume and Issue: 362(6413)
Published: Oct. 26, 2018
The spatial organization of chromatin is pivotal for regulating genome functions. We report an imaging method tracing with kilobase- and nanometer-scale resolution, unveiling conformation across topologically associating domains (TADs) in thousands individual cells. Our data revealed TAD-like structures globular sharp domain boundaries single varied from cell to cell, occurring nonzero probabilities at all genomic positions but preferentially CCCTC-binding factor (CTCF)- cohesin-binding sites. Notably, cohesin depletion, which abolished TADs the population-average level, did not diminish cells eliminated preferential boundary positions. Moreover, we observed widespread, cooperative, multiway interactions, remained after depletion. These results provide critical insight into mechanisms underlying hub formation.
Language: Английский
Citations
888
Science, Journal Year: 2017, Volume and Issue: 357(6349)
Published: July 27, 2017
A close-up view inside the nucleus The nuclei of human cells contain 2 meters genomic DNA. How does it all fit? Compaction starts with DNA wrapping around histone octamers to form nucleosomes, but is unclear how these further compress into mitotic chromosomes. Ou et al. describe a DNA-labeling method that allows them visualize chromatin organization in (see Perspective by Larson and Misteli). They show forms flexible chains diameters between 5 24 nm. In chromosomes, bend back on themselves pack at high density, whereas during interphase, are more extended. Science , this issue p. eaag0025 ; see also 354
Language: Английский
Citations
810
Molecular Cell, Journal Year: 2016, Volume and Issue: 62(5), P. 668 - 680
Published: June 1, 2016
Language: Английский
Citations
772
Nature, Journal Year: 2017, Volume and Issue: 547(7661), P. 61 - 67
Published: July 1, 2017
Language: Английский
Citations
741