DNA entry, exit and second DNA capture by cohesin: insights from biochemical experiments

Murayama, Yasuto

doi:10.1080/19491034.2018.1516486

Cited by 5 publications

(4 citation statements)

References 84 publications

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“…As a highly conserved zinc finger protein, CTCF plays crucial roles in transcriptional activation/repression, insulation, and the formation of higher‐order chromatin structures 62,63 . Due to the DNA sequences that bind CTCF being asymmetric, CTCF located at TADs boundaries has directionality 64,65 . In over 90% of TADs, CTCF sites are situated at boundaries in a convergent orientation 66 .…”

Section: D Genome Structurementioning

confidence: 99%

“… 62 , 63 Due to the DNA sequences that bind CTCF being asymmetric, CTCF located at TADs boundaries has directionality. 64 , 65 In over 90% of TADs, CTCF sites are situated at boundaries in a convergent orientation. 66 CRISPR‐edited inversions of CTCF binding sequences disrupt TAD structure and cause abnormal gene expression, suggesting that CTCF orientation is important for TAD.…”

Section: D Genome Structurementioning

confidence: 99%

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Three‐dimensional genome structure and function

Líu

Tsai

Yang

et al. 2023

MedComm

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Linear DNA undergoes a series of compression and folding events, forming various three‐dimensional (3D) structural units in mammalian cells, including chromosomal territory, compartment, topologically associating domain, and chromatin loop. These structures play crucial roles in regulating gene expression, cell differentiation, and disease progression. Deciphering the principles underlying 3D genome folding and the molecular mechanisms governing cell fate determination remains a challenge. With advancements in high‐throughput sequencing and imaging techniques, the hierarchical organization and functional roles of higher‐order chromatin structures have been gradually illuminated. This review systematically discussed the structural hierarchy of the 3D genome, the effects and mechanisms of cis‐regulatory elements interaction in the 3D genome for regulating spatiotemporally specific gene expression, the roles and mechanisms of dynamic changes in 3D chromatin conformation during embryonic development, and the pathological mechanisms of diseases such as congenital developmental abnormalities and cancer, which are attributed to alterations in 3D genome organization and aberrations in key structural proteins. Finally, prospects were made for the research about 3D genome structure, function, and genetic intervention, and the roles in disease development, prevention, and treatment, which may offer some clues for precise diagnosis and treatment of related diseases.

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Section: D Genome Structurementioning

confidence: 99%

Section: D Genome Structurementioning

confidence: 99%

Three‐dimensional genome structure and function

Líu

Tsai

Yang

et al. 2023

MedComm

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“…Cohesin is an evolutionarily conserved ring-shaped protein complex (reviewed in refs. 21 , 22 ) that encircles pairs of replicated chromosomes, known as sister chromatids, allowing recognition of the sister chromatids for segregation during both mitosis and meiosis 23 , 24 . Sister chromatid cohesion mediated by cohesin is essential for faithful chromosome segregation during cell divisions 25 – 27 .…”

Section: Introductionmentioning

confidence: 99%

Disruption of NIPBL/Scc2 in Cornelia de Lange Syndrome provokes cohesin genome-wide redistribution with an impact in the transcriptome

et al. 2021

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Cornelia de Lange syndrome (CdLS) is a rare disease affecting multiple organs and systems during development. Mutations in the cohesin loader, NIPBL/Scc2, were first described and are the most frequent in clinically diagnosed CdLS patients. The molecular mechanisms driving CdLS phenotypes are not understood. In addition to its canonical role in sister chromatid cohesion, cohesin is implicated in the spatial organization of the genome. Here, we investigate the transcriptome of CdLS patient-derived primary fibroblasts and observe the downregulation of genes involved in development and system skeletal organization, providing a link to the developmental alterations and limb abnormalities characteristic of CdLS patients. Genome-wide distribution studies demonstrate a global reduction of NIPBL at the NIPBL-associated high GC content regions in CdLS-derived cells. In addition, cohesin accumulates at NIPBL-occupied sites at CpG islands potentially due to reduced cohesin translocation along chromosomes, and fewer cohesin peaks colocalize with CTCF.

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“…SMC subunits (SMC1, SMC3 in cohesin and SMC2, SMC4 in condensin) fold back on themselves to form approximately a 50nm long arm. These two arms are then connected at one end by a hinge domain and other two ends which have ATPase activity are connected by a kleisin subunit (RAD21 in cohesin and condensin-associated protein H2 [CAPH2] in condensin)to form a ring like structure of the whole complex [5, 21, 26, 27, 42, 43, 48]. This ring like structure has been hypothesized to form a topological association with the DNA backbone [38, 46].…”

Section: Introductionmentioning

confidence: 99%

The accidental ally: Nucleosomal barriers can accelerate cohesin mediated loop formation in chromatin

Maji¹,

Padinhateeri²,

Mitra³

2019

Preprint

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An important question in the context of the 3D organization of chromosomes is the mechanism of formation of large loops between distant base pairs. Recent experiments suggest that the formation of loops might be mediated by Loop Extrusion Factor proteins like cohesin. Experiments on cohesin have shown that cohesins walk diffusively on the DNA, and that nucleosomes act as obstacles to the diffusion, lowering the permeability and hence reducing the effective diffusion constant. An estimation of the times required to form the loops of typical sizes seen in Hi-C experiments using these low effective diffusion constants leads to times that are unphysically large. The puzzle then is the following, how does a cohesin molecule diffusing on the DNA backbone achieve speeds necessary to form the large loops seen in experiments? We propose a simple answer to this puzzle, and show that while at low densities, nucleosomes act as barriers to cohesin diffusion, beyond a certain concentration, they can reduce loop formation times due to a subtle interplay between the nucleosome size and the mean linker length. This effect is further enhanced on considering stochastic binding kinetics of nucleosomes on the DNA backbone, and leads to predictions of lower loop formation times than might be expected from a naive obstacle picture of nucleosomes. 2 structure inside the nucleus remains an important open question [16, 40, 41, 62]. An 3 ubiquitous structural motif, as observed through 14, 25, 47] and other 4 experiments [34, 36, 50] are the formation of large loops, ranging from kilobases to 5 megabases. These loops play both a structural as well as functional roles, bringing 6 together regions of the DNA that are widely spaced along the backbone [1, 9, 35]. In 7 recent years, much work has been done in trying to understand the mechanism of 8 formation of these large loops. There is now a significant body of experimental 9 observations that implicate a class of proteins called the Structural maintenance of 10 chromosome (SMC) protein complexes -such as cohesin and condensin in the formation 11 and maintenance of these large chromosomal loops [19, 20, 28, 33, 54, 55, 58, 59, 64]. 12 Structural maintenance of chromosome (SMC) protein complexes are known to play 13 a major role in chromosome segregation in interphase and mitosis . Both cohesin and 14 condensin consists of SMC subunits and share structural similarities. SMC subunits 15 1/15 (SMC1, SMC3 in cohesin and SMC2, SMC4 in condensin) fold back on themselves to 16 form approximately a 50nm long arm. These two arms are then connected at one end 17 by a hinge domain and other two ends which have ATPase activity are connected by a 18 kleisin subunit (RAD21 in cohesin and condensin-associated protein H2 [CAPH2] in 19condensin)to form a ring like structure of the whole complex [5, 21, 26, 27, 42, 43, 48]. 20This ring like structure has been hypothesized to form a topological association with the 21 DNA backbone [38, 46]. In particular, experiments on cohesin have shown that such 22 topol...

show abstract

DNA entry, exit and second DNA capture by cohesin: insights from biochemical experiments

Cited by 5 publications

References 84 publications

Three‐dimensional genome structure and function

Three‐dimensional genome structure and function

Disruption of NIPBL/Scc2 in Cornelia de Lange Syndrome provokes cohesin genome-wide redistribution with an impact in the transcriptome

The accidental ally: Nucleosomal barriers can accelerate cohesin mediated loop formation in chromatin

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