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1.
Phys Rev E ; 107(6-1): 064406, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37464651

ABSTRACT

Loop extrusion by motor proteins mediates the attractive interactions in chromatin on the length scale of megabases, providing the polymer with a well-defined structure and at the same time determining its dynamics. The mean-square displacement of chromatin loci varies from a Rouse-like scaling to a more constrained subdiffusion, depending on cell type, genomic region, and time scale. With a simple polymeric model, we show that such a Rouse-like dynamics occurs when the parameters of the model are chosen so that contacts are local along the chain, while in the presence of nonlocal contacts we observe subdiffusion at short time scales with exponents smaller than 0.5. Such exponents are independent of the detailed choice of the parameters and build a master curve that depends only on the mean locality of the resulting contacts. We compare the loop-extrusion model with a polymeric model with static links, showing that also in this case only the presence of nonlocal contacts can produce low-exponent subdiffusion. We interpret these results in terms of a simple analytical model.


Subject(s)
Chromatin , Polymers , Polymers/chemistry
2.
Nat Genet ; 54(12): 1907-1918, 2022 12.
Article in English | MEDLINE | ID: mdl-36471076

ABSTRACT

In mammals, interactions between sequences within topologically associating domains enable control of gene expression across large genomic distances. Yet it is unknown how frequently such contacts occur, how long they last and how they depend on the dynamics of chromosome folding and loop extrusion activity of cohesin. By imaging chromosomal locations at high spatial and temporal resolution in living cells, we show that interactions within topologically associating domains are transient and occur frequently during the course of a cell cycle. Interactions become more frequent and longer in the presence of convergent CTCF sites, resulting in suppression of variability in chromosome folding across time. Supported by physical models of chromosome dynamics, our data suggest that CTCF-anchored loops last around 10 min. Our results show that long-range transcriptional regulation might rely on transient physical proximity, and that cohesin and CTCF stabilize highly dynamic chromosome structures, facilitating selected subsets of chromosomal interactions.


Subject(s)
Chromosomes , Chromosomes/genetics
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