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

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

doi:10.1016/j.molcel.2022.10.002

Cited by 8 publications

(16 citation statements)

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“…To analyze somatic cells, we used worms in the early L3 stage, at which point most somatic cells have stopped dividing and the germline has not started proliferating (32). To knock down cohesin specifically in the somatic cells, we used the background strain in which the auxin response gene TIR1 is under the control of a soma-specific promoter eft-3 (30, 31). This background strain is used as a control where TIR1 is expressed but none of the endogenous genes are tagged with degron-gfp (Figure 1B).…”

Section: Resultsmentioning

confidence: 99%

“…Unlike mammalian systems where TADs are observed on all chromosomes, in C. elegans , autosomes do not display stereotypical loop-anchored TADs with defined boundaries (Crane et al 2015; Bian et al 2020; Sawh and Mango 2022). Instead, loop-anchored TADs are formed on the X chromosomes by an X-specific condensin complex (Anderson et al 2019; Kim et al 2022; Morao et al 2022). Like the mammalian cohesin complex, condensin mediated TADs on the C. elegans X chromosomes are mega base pairs (Mb) in scale.…”

Section: Resultsmentioning

confidence: 99%

“…It is possible that these specific proteins or their downstream effects, such as DNA topology regulate loop extrusion. Indeed C. elegans condensin DC requires topoisomerase II for its long-range processivity (30). We noticed that the asymmetry of our example jet in Figure 3 stems from stronger cohesin loop extrusion to the left side, where there is a long gene that is highly transcribed (Figure 3A).…”

Section: Discussionmentioning

confidence: 99%

“…frequent switching of direction in a one-sided extrusion scheme), effect of cohesin molecules meeting one another (resulting in bypassing to form secondary folds in loops or colliding and stopping extrusion on one side), and specific proteins controlling loop extrusion as loader/facilitator (NIPBL), remover (WAPL), or acting as barriers (e.g. MCM complex, RNA Pol II, DNA topology) (Dequeker et al 2022; Morao et al 2022; Banigan et al 2023; Corsi et al 2023).…”

Section: Introductionmentioning

confidence: 99%

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Cohesin organizes 3D DNA contacts surrounding active enhancers inC. elegans

Kim,

Wang,

Ercan

2023

Preprint

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In mammals, cohesin and CTCF organize the 3D genome into topologically associated domains (TADs) to regulate communication between cis-regulatory elements. However, many organisms, including S. cerevisiae, C. elegans, and A. thaliana lack CTCF. Here, we use C. elegans as a model to investigate the function of cohesin in 3D genome organization in an animal without CTCF. We use auxin-inducible degradation to acutely deplete SMC-3 or its negative regulator WAPL-1 from somatic cells. Using Hi-C data, we identify a cohesin-dependent 3D genome feature termed chromatin jets (aka fountains), also observed in zebrafish and mammalian genomes. The jets emerge from NIPBL occupied segments, and the trajectory of the jets coincides with cohesin binding. The spreading of cohesin from jet origins depends on a fully intact cohesin complex and is extended upon WAPL-1 depletion. These results support the idea that cohesin is preferentially loaded at NIPBL occupied sites, from which cohesin loop extrudes in an effectively two-sided manner. The location of putative loading sites coincides with active enhancers and the pattern of chromatin jets correlates with transcription. We propose that in the absence of CTCF, preferential loading of cohesin at enhancers is a conserved mechanism of genome organization that regulates the interaction of gene regulatory elements in 3D.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cohesin organizes 3D DNA contacts surrounding active enhancers inC. elegans

Kim,

Wang,

Ercan

2023

Preprint

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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 (Erceg et al 2019; AlHaj Abed et al 2019), yeast (Schalbetter et al 2017, 2019), nematodes (Morao et al 2021), chicken (Gibcus et al 2018)) and cellular states (mitosis (Abramo et al 2019; Gibcus et al 2018), meiosis (Zuo et al 2021; Schalbetter et al 2019)). 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: Modulesmentioning

confidence: 99%

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

Abdennur

Abraham

Fudenberg

et al. 2022

Preprint

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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. 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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