Organization of Chromosomal DNA by SMC Complexes

Yatskevich, Stanislau; Rhodes, James; Nasmyth, Kim

doi:10.1146/annurev-genet-112618-043633

Cited by 281 publications

(325 citation statements)

References 208 publications

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“…The models, which also assume that MukBEF loads randomly on all chromosomal regions, explain how MukBEF clusters colocalize with the replication origin region (oriC) in wild-type cells, while MukBEF clusters localize equally with all genetic regions tested in MatP − cells. (Kakui and Uhlmann 2018;Wani et al 2018;Paul et al 2019;Yatskevich et al 2019) Is the MukBEF-organized E. coli chromosome placed randomly within a cell? Early imaging studies showed that in new-born E. coli cells that have not initiated replication, the left and right replichores are organized into separate cell halves, while oriC is at midcell (Wang et al 2006).…”

Section: Chromosome Organization In E Coli and Other Bacteriamentioning

confidence: 99%

SMC complexes organize the bacterial chromosome by lengthwise compaction

Mäkelä

Sherratt

2020

Curr Genet

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Structural maintenance of chromosomes (SMC) complexes are ancient and conserved molecular machines that organize chromosomes in all domains of life. We propose that the principles of chromosome folding needed to accommodate DNA inside a cell in an accessible form will follow similar principles in prokaryotes and eukaryotes. However, the exact contributions of SMC complexes to bacterial chromosome organization have been elusive. Recently, it was shown that the SMC homolog, MukBEF, organizes and individualizes the Escherichia coli chromosome by forming a filamentous axial core from which DNA loops emanate, similar to the action of condensin in mitotic chromosome formation. MukBEF action, along with its interaction with the partner protein, MatP, also facilitates chromosome individualization by directing opposite chromosome arms (replichores) to different cell halves. This contrasts with the situation in many other bacteria, where SMC complexes organise chromosomes in a way that the opposite replichores are aligned along the long axis of the cell. We highlight the similarities and differences of SMC complex contributions to chromosome organization in bacteria and eukaryotes, and summarize the current mechanistic understanding of the processes.

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Section: Chromosome Organization In E Coli and Other Bacteriamentioning

confidence: 99%

SMC complexes organize the bacterial chromosome by lengthwise compaction

Mäkelä

Sherratt

2020

Curr Genet

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“…Cohesin is a highly conserved chromosome-associated multi-subunit ring-shaped ATPase complex built upon subunits belonging to the structural maintenance of chromosomes (Smc) family and is important for diverse chromosome-based processes [28][29][30][31][32][33] .…”

Section: Upon Binding a Recombination Center (Rcmentioning

confidence: 99%

“…Remarkably, while CTCF degradation suppressed most CBE-based chromatin interactions, it promoted robust RC interactions with, and robust VH-to-DJH joining of, distal VHs, with patterns similar to those of "locus-contracted" primary pro-B cells. Thus, downmodulation of CTCF-bound scanning-impediment activity promotes cohesin-driven RAG-scanning across the 2.7Mb Igh locus.Cohesin is a highly conserved chromosome-associated multi-subunit ring-shaped ATPase complex built upon subunits belonging to the structural maintenance of chromosomes (Smc) family and is important for diverse chromosome-based processes [28][29][30][31][32][33] .The cohesin complex is proposed to form contact loop domains by extrusion of chromatin until reaching convergent CTCF-bound CBE anchors 2-10 . In this regard, cohesin extrudes both naked and nucleosome-containing DNA in an NIPBL-MAU2 and ATP-hydrolysisdependent manner in vitro 34,35 .…”

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confidence: 99%

CTCF orchestrates long-range cohesin-driven V(D)J recombinational scanning

Lou

Dring

et al. 2020

Preprint

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RAG endonuclease initiates V(D)J recombination in progenitor (pro)-B cells 1 . Upon binding a recombination center (RC)-based JH, RAG scans upstream chromatin via loop extrusion, potentially mediated by cohesin 2-10 , to locate Ds and assemble a DJH-based RC 11 . CTCF looping factor-bound elements (CBEs) within IGCR1 upstream of Ds impede RAG-scanning 12-15 ; but their inactivation allows scanning to proximal VHs where additional CBEs activate rearrangement and impede scanning any further upstream 15,16 . Distal VH utilization is thought to involve diffusional RC access following large-scale Igh locus contraction 17-23 . Here, we test the potential of linear RAG-scanning to mediate distal VH usage in G1-arrested, v-Abl-pro-B cell lines 24,25 , which undergo robust D-to-JH but little VH-to-DJH rearrangements, presumably due to lack of locus contraction 11,15 . Through an auxin-inducible approach 26,27 , we degrade the cohesin-component Rad21 4,7,27 or CTCF 7,9 in these G1-arrested lines, which maintain substantial viability throughout four-day experiments. Rad21 degradation eliminated all V(D)J recombination and RAG-scanning-associated interactions, except RC-located DQ52-to-JH joining in which synapsis occurs by diffusion 11 . Remarkably, while CTCF degradation suppressed most CBE-based chromatin interactions, it promoted robust RC interactions with, and robust VH-to-DJH joining of, distal VHs, with patterns similar to those of "locus-contracted" primary pro-B cells. Thus, downmodulation of CTCF-bound scanning-impediment activity promotes cohesin-driven RAG-scanning across the 2.7Mb Igh locus.Cohesin is a highly conserved chromosome-associated multi-subunit ring-shaped ATPase complex built upon subunits belonging to the structural maintenance of chromosomes (Smc) family and is important for diverse chromosome-based processes [28][29][30][31][32][33] .The cohesin complex is proposed to form contact loop domains by extrusion of chromatin until reaching convergent CTCF-bound CBE anchors 2-10 . In this regard, cohesin extrudes both naked and nucleosome-containing DNA in an NIPBL-MAU2 and ATP-hydrolysisdependent manner in vitro 34,35 . Our studies implicated the cohesin complex in chromatin loop extrusion-mediated mechanisms of lymphocyte V(D)J and IgH class switch recombination 11,[14][15][16]36,37 . To further elucidate potential cohesin role(s) in chromatin scanning during long-range V(D)J recombination, we employed a mini auxin-inducible degron (mAID) approach 4,7,26,27 to conditionally degrade Rad21, a core component of the cohesin complex,in v-Abl-kinase-transformed, Eµ-Bcl2-expressing mouse pro-B cells ("v-Abl pro-B cells").

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“…Cohesin complex may extrude chromatin fiber individually [70] and asymmetrically [71,72], or may even use the "inchworm" model [72,73]. For clarity, we assume that cohesin loop extrusion with "two heads" as previously proposed [19].…”

Section: "Two-headed" Cohesin Loop Extrusionmentioning

confidence: 99%

Tandem CTCF sites function as insulators to balance spatial chromatin contacts and topological enhancer-promoter selection

Jia

et al. 2020

Genome Biol

114

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Background: CTCF is a key insulator-binding protein, and mammalian genomes contain numerous CTCF sites, many of which are organized in tandem. Results: Using CRISPR DNA-fragment editing, in conjunction with chromosome conformation capture, we find that CTCF sites, if located between enhancers and promoters in the protocadherin (Pcdh) and β-globin clusters, function as an enhancer-blocking insulator by forming distinct directional chromatin loops, regardless whether enhancers contain CTCF sites or not. Moreover, computational simulation in silico and genetic deletions in vivo as well as dCas9 blocking in vitro revealed balanced promoter usage in cell populations and stochastic monoallelic expression in single cells by large arrays of tandem CTCF sites in the Pcdh and immunoglobulin heavy chain (Igh) clusters. Furthermore, CTCF insulators promote, counter-intuitively, long-range chromatin interactions with distal directional CTCF sites, consistent with the cohesin "loop extrusion" model. Finally, gene expression levels are negatively correlated with CTCF insulators located between enhancers and promoters on a genome-wide scale. Thus, single CTCF insulators ensure proper enhancer insulation and promoter activation while tandem CTCF topological insulators determine balanced spatial contacts and promoter choice.Conclusions: These findings have interesting implications on the role of topological chromatin insulators in 3D genome folding and developmental gene regulation.

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Organization of Chromosomal DNA by SMC Complexes

Cited by 281 publications

References 208 publications

SMC complexes organize the bacterial chromosome by lengthwise compaction

SMC complexes organize the bacterial chromosome by lengthwise compaction

CTCF orchestrates long-range cohesin-driven V(D)J recombinational scanning

Tandem CTCF sites function as insulators to balance spatial chromatin contacts and topological enhancer-promoter selection

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