Extensive mutual influences of SMC complexes shape 3D genome folding
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ABSTRACT:
PROVIDER: PRJNA1124163 | ENA |
REPOSITORIES: ENA
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Project description:Mammalian genomes are folded by the distinct actions of SMC complexes which include the chromatin loop-extruding cohesin, the sister-chromatid cohesive cohesin, and the mitotic chromosome-associated condensins 1-3. While these complexes function at different stages of the cell cycle, they co-exist on chromatin during the G2/M-phase transition, when genome structure undergoes a dramatic reorganization 1,2. Yet, how distinct SMC complexes affect each other and how their mutual interplay orchestrates the dynamic folding of 3D genome remains elusive. Here, we engineered all possible cohesin/condensin configurations on mitotic chromosomes to delineate the concerted, mutually influential action of SMC complexes. We find that: (i) Condensin disrupts extrusive-cohesin binding at CTCF sites, thereby promoting the disassembly of interphase TADs and loops during mitotic progression. Conversely, extrusive-cohesin impedes condensin mediated mitotic chromosome spiralization. (ii) Condensin diminishes cohesive-cohesin peaks and, conversely, cohesive-cohesin antagonizes condensin-mediated mitotic chromosome longitudinal shortening. Co-presence of extrusive- and cohesive-cohesin synergizes these effects and dramatically inhibits mitotic chromosome condensation. (iii) Extrusive-cohesin positions cohesive-cohesin at CTCF binding sites. However, cohesive-cohesin by itself cannot be arrested by CTCF molecules, is insufficient to establish TADs or loops and lacks loop extrusion capacity, implying non-overlapping function with extrusive-cohesin. (iv) Cohesive-cohesin restricts extrusive-cohesin mediated chromatin loop expansion. Collectively, our data describe a comprehensive three-way interplay among major SMC complexes that dynamically sculpts chromatin architecture during cell cycle progression.
2024-12-21 | GSE269952 | GEO
Project description:Extensive folding variability between homologous chromosomes in mammalian cells
| PRJNA1071571 | ENA
Project description:Extensive folding variability between homologous chromosomes in mammalian cells [GAM]
| PRJNA1071570 | ENA
Project description:Extensive folding variability between homologous chromosomes in mammalian cells [RNA-seq]
| PRJNA1071503 | ENA
Project description:Extensive folding variability between homologous chromosomes in mammalian cells [ChIP-Seq]
| PRJNA1071563 | ENA
Project description:Genetic variation and 3D chromatin structure have major roles in gene regulation. Structural differences between genotypically different chromosomes and their effects on gene expression remain ill understood, due to challenges in mapping 3D genome structure with allele-specific resolution. Here, we applied Genome Architecture Mapping (GAM) to a hybrid mouse embryonic stem cell (ESC) line with high SNP density. Given its high efficiency of haplotype phasing, GAM resolves allele-specific 3D genome structures with high sensitivity. We discovered extensive genotype-specific folding of chromosomes in compartments, topologically associating domains (TADs), long-range enhancer-promoter contacts and CTCF loops, often coinciding with allele-specific gene expression in association with Polycomb repression. We show that histone genes are expressed with allelic imbalance and involved in allele-specific chromatin contacts marked by H3K27me3. Functional analysis through conditional Ezh2- or Ring1b-knockdown shows a role for Polycomb repression in tuning histone protein levels. Our work reveals that the homologous chromosomes have highly distinct 3D folding structures, and their intricate relationships with gene-specific mechanisms of allelic expression imbalance.
2025-01-29 | GSE254717 | GEO
Project description:Structural maintenance of chromosomes (SMC) complexes fold genomes by extruding DNA loops. In eukaryotes, loop-extruding SMC complexes form topologically associating domains (TADs) by being stalled by roadblock proteins. It remains unclear whether a similar mechanism of domain formation exists in prokaryotes. Using high-resolution chromosome conformation capture sequencing, we show that an archaeal homolog of the bacterial Smc-ScpAB complex organizes the genome of Thermococcus kodakarensis into TAD-like domains. We also find that TrmBL2, a nucleoid-associated protein that forms a stiff nucleoprotein filament, stalls the T. kodakarensis SMC complex and establishes a boundary at the site-specific recombination site dif. TrmBL2 stalls the SMC complex at tens of additional non-boundary loci with lower efficiency. Intriguingly, the stalling efficiency is correlated with shape properties of underlying DNA sequences. Our study illuminates not only a eukaryotic-like mechanism of domain formation in archaea, but also an unforeseen role of intrinsic DNA shape in large-scale genome organization.
2024-12-15 | GSE267297 | GEO
Project description:Structural maintenance of chromosomes (SMC) complexes fold genomes by extruding DNA loops. In eukaryotes, loop-extruding SMC complexes form topologically associating domains (TADs) by being stalled by roadblock proteins. It remains unclear whether a similar mechanism of domain formation exists in prokaryotes. Using high-resolution chromosome conformation capture sequencing, we show that an archaeal homolog of the bacterial Smc-ScpAB complex organizes the genome of Thermococcus kodakarensis into TAD-like domains. We also find that TrmBL2, a nucleoid-associated protein that forms a stiff nucleoprotein filament, stalls the T. kodakarensis SMC complex and establishes a boundary at the site-specific recombination site dif. TrmBL2 stalls the SMC complex at tens of additional non-boundary loci with lower efficiency. Intriguingly, the stalling efficiency is correlated with shape properties of underlying DNA sequences. Our study illuminates not only a eukaryotic-like mechanism of domain formation in archaea, but also an unforeseen role of intrinsic DNA shape in large-scale genome organization.
2024-12-15 | GSE267299 | GEO
Project description:Structural maintenance of chromosomes (SMC) complexes fold genomes by extruding DNA loops. In eukaryotes, loop-extruding SMC complexes form topologically associating domains (TADs) by being stalled by roadblock proteins. It remains unclear whether a similar mechanism of domain formation exists in prokaryotes. Using high-resolution chromosome conformation capture sequencing, we show that an archaeal homolog of the bacterial Smc-ScpAB complex organizes the genome of Thermococcus kodakarensis into TAD-like domains. We also find that TrmBL2, a nucleoid-associated protein that forms a stiff nucleoprotein filament, stalls the T. kodakarensis SMC complex and establishes a boundary at the site-specific recombination site dif. TrmBL2 stalls the SMC complex at tens of additional non-boundary loci with lower efficiency. Intriguingly, the stalling efficiency is correlated with shape properties of underlying DNA sequences. Our study illuminates not only a eukaryotic-like mechanism of domain formation in archaea, but also an unforeseen role of intrinsic DNA shape in large-scale genome organization.
2024-12-15 | GSE267298 | GEO
Project description:Chromosome organization by structural maintenance of chromosomes (SMC) complexes is vital to living organisms. SMC complexes were recently found to be motors that extrude DNA loops. However, it remains unclear what happens when multiple complexes encounter one another in vivo on the same DNA and how interactions help organize an active genome. We created a crash-course track system to study SMC complex encounters in vivo by engineering the Bacillus subtilis chromosome to have defined SMC loading sites. Chromosome conformation capture (Hi-C) analyses of over 20 engineered strains show an amazing variety of never-before-seen chromosome folding patterns. Via 3D polymer simulations and theory, we find that these patterns require SMC complexes to bypass each other in vivo, as recently seen in an in vitro study. We posit that the bypassing activity enables SMC complexes to spatially organize a functional and busy genome.
2021-06-10 | GSE155279 | GEO