Topoisomerases I and II facilitate condensin DC translocation to organize and repress X chromosomes in <i>C. elegans</i>

Morao, Ana Karina; Kim, Jun; Obaji, Daniel; Sun, Siyu; Ercan, Sevinç

doi:10.1101/2021.11.30.470639

Cited by 5 publications

(4 citation statements)

References 91 publications

(148 reference statements)

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“…Alternatively, condensin DC loop extrusion is a mechanism evolved to distribute the complex across long distances from the rex sites to accomplish chromosome-wide dosage compensation. Consistent with this idea, upon top-2 depletion, the processivity of condensin DC loop extrusion reduces, and the spreading of the complex to the chromosome also reduces [79]. The repressive effect of condensin DC may be local and loop extrusion independent.…”

Section: Discussionmentioning

confidence: 94%

Condensin DC loads and spreads from recruitment sites to create loop-anchored TADs inC. elegans

Jimenez

Kim

Ragipani

et al. 2021

Preprint

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Condensins are molecular motors that compact DNA for chromosome segregation and gene regulation. In vitro experiments have begun to elucidate the mechanics of condensin function but how condensin loading and translocation along DNA controls eukaryotic chromosome structure in vivo remains poorly understood. To address this question, we took advantage of a specialized condensin, which organizes the 3D conformation of X chromosomes to mediate dosage compensation (DC) in C. elegans. Condensin DC is recruited and spreads from a small number of recruitment elements on the X chromosome (rex). We found that ectopic insertion of rex sites on an autosome leads to bidirectional spreading of the complex over hundreds of kilobases. On the X chromosome, strong rex sites contain multiple copies of a 12-bp sequence motif and act as TAD borders. Inserting a strong rex and ectopically recruiting the complex on the X chromosome or an autosome creates a loop-anchored TAD. Unlike the CTCF system, which controls TAD formation by cohesin, direction of the 12-bp motif does not control the specificity of loops. In an X;V fusion chromosome, condensin DC linearly spreads into V and increases 3D DNA contacts, but fails to form TADs in the absence of rex sites. Finally, we provide in vivo evidence for the loop extrusion hypothesis by targeting multiple dCas9-Suntag complexes to an X chromosome repeat region. Consistent with linear translocation along DNA, condensin DC accumulates at the block site. Together, our results support a model whereby strong rex sites act as insulation elements through recruitment and bidirectional spreading of condensin DC molecules and form loop-anchored TADs.

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Section: Discussionmentioning

confidence: 94%

Condensin DC loads and spreads from recruitment sites to create loop-anchored TADs inC. elegans

Jimenez

Kim

Ragipani

et al. 2021

Preprint

Self Cite

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“…The main cooltools modules were initially developed with mammalian interphase Hi-C maps in mind, but the flexible implementation of cooltools has made it useful for analysis of data from different organisms (e.g., Drosophila [ 17 , 18 ], yeast [ 19 , 20 ], nematodes [ 21 ], chicken [ 22 ]) and cellular states (mitosis [ 22 , 23 ], meiosis [ 20 , 24 ]). We explain cooltools in tripartite chapters for each module below, describing the relevant features, the implementation, and analyses where the flexible API has proven useful.…”

Section: Resultsmentioning

confidence: 99%

Cooltools: Enabling high-resolution Hi-C analysis in Python

Abdennur,

Abraham,

Fudenberg

et al. 2024

PLoS Comput Biol

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Chromosome conformation capture (3C) technologies reveal the incredible complexity of genome organization. Maps of increasing size, depth, and resolution are now used to probe genome architecture across cell states, types, and organisms. Larger datasets add challenges at each step of computational analysis, from storage and memory constraints to researchers’ time; however, analysis tools that meet these increased resource demands have not kept pace. Furthermore, existing tools offer limited support for customizing analysis for specific use cases or new biology. Here we introduce cooltools (https://github.com/open2c/cooltools), a suite of computational tools that enables flexible, scalable, and reproducible analysis of high-resolution contact frequency data. Cooltools leverages the widely-adopted cooler format which handles storage and access for high-resolution datasets. Cooltools provides a paired command line interface (CLI) and Python application programming interface (API), which respectively facilitate workflows on high-performance computing clusters and in interactive analysis environments. In short, cooltools enables the effective use of the latest and largest genome folding datasets.

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“…Recent work suggests that transcription-induced supercoiling of DNA upon depletion of topoisomerase I leads to accumulation of condensin I DC in gene bodies, and that this effect increases with gene length (Morao et al 2021). We analyzed whether cleavage of the different SMCs differentially affected genes of different lengths, by comparing the LFC as a function of gene expression in the TEV control strain and gene length (Fig.…”

Section: Resultsmentioning

confidence: 99%

Condensin I folds theC. elegansgenome

Das

Semple

Volodkina

et al. 2022

Preprint

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Structural Maintenance of Chromosomes (SMC) complexes, cohesin and condensins, were named for their roles in meiotic and mitotic chromosome separation and compaction. Recent data from mammalian cells and Drosophila have described additional roles for cohesin in folding the interphase genome into loops and domains. However, determinants of genome folding in holocentric species remain unclear. Using high-resolution chromosome conformation capture, we show that C. elegans chromosomes exhibit two types of compartments: a large-scale compartmentalization that corresponds to central vs telomere proximal regions and a small-scale compartmentalization that reflects epigenomic states. By systematically and acutely inactivating each SMC complex, we find that in contrast to other organisms, condensin I plays a major role in long-range genome folding, while cohesin creates small loops. Loss of condensin I causes genome-wide decompaction, chromosome mixing, and disappearance of TAD structures, while reinforcing fine-scale epigenomic compartments. Counter-intuitively, the removal of condensin I and its X-specific variant condensin IDC from the X chromosomes reveals the existence of a third compartment grouping together a subset of previously characterized loading sites for condensin IDC and binding sites for the X-targeting complex SDC. While transcriptional changes were minor for all autosomes upon cohesin, condensin II, and condensin I/IDC inactivation, removal of condensin I/IDC from the X chromosome led to transcriptional up-regulation of X-linked genes. In conclusion, we describe a novel function for C. elegans condensin I/IDC in holocentric interphase chromosome organization, which substitutes the role played by cohesin in other organisms.

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Topoisomerases I and II facilitate condensin DC translocation to organize and repress X chromosomes in C. elegans

Cited by 5 publications

References 91 publications

Condensin DC loads and spreads from recruitment sites to create loop-anchored TADs inC. elegans

Condensin DC loads and spreads from recruitment sites to create loop-anchored TADs inC. elegans

Cooltools: Enabling high-resolution Hi-C analysis in Python

Condensin I folds theC. elegansgenome

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