Hi-C analyses with GENOVA: a case study with cohesin variants

Weide, Robin H. van der; Brand, Teun van den; Haarhuis, Judith H.I.; Teunissen, Hans; Rowland, Benjamin D.; Wit, Elzo de

doi:10.1093/nargab/lqab040

Cited by 79 publications

(58 citation statements)

References 59 publications

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“…To obtain an additional description of the global trends of contact probabilities in wild-type and SETDB1-depleted macrophages, we generated aggregate plots displaying Hi-C contact probabilities ( Flyamer et al 2017 ; van der Weide et al 2021 ). Plots were centered on the summit of induced or not-induced CTCF peaks that were either at insulation sites ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Relative contact probability (RCP), aggregate region analysis (ARA), aggregate peak analysis (APA), and aggregate TAD analysis (ATA) were performed using the R library GENOVA ( van der Weide et al 2021 ) after importing individual iced normalized contact matrices at different resolutions. As specified in each figure legend, either individual samples or the average contact matrices between replicates were used and displayed.…”

Section: Methodsmentioning

confidence: 99%

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H3K9 trimethylation in active chromatin restricts the usage of functional CTCF sites in SINE B2 repeats

et al. 2022

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Six methyltransferases divide labor in establishing genomic profiles of histone H3 lysine 9 methylation (H3K9me), an epigenomic modification controlling constitutive heterochromatin, gene repression, and silencing of retroelements. Among them, SETDB1 is recruited to active chromatin domains to silence the expression of endogenous retroviruses. In the context of experiments aimed at determining the impact of SETDB1 on stimulus-inducible gene expression in macrophages, we found that loss of H3K9me3 caused by SETDB1 depletion was associated with increased recruitment of CTCF to >1600 DNA binding motifs contained within SINE B2 repeats, a previously unidentified target of SETDB1-mediated repression. CTCF is an essential regulator of chromatin folding that restrains DNA looping by cohesin, thus creating boundaries among adjacent topological domains. Increased CTCF binding to SINE B2 repeats enhanced insulation at hundreds of sites and increased loop formation within topological domains containing lipopolysaccharide-inducible genes, which correlated with their impaired regulation in response to stimulation. These data indicate a role of H3K9me3 in restraining genomic distribution and activity of CTCF, with an impact on chromatin organization and gene regulation.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

H3K9 trimethylation in active chromatin restricts the usage of functional CTCF sites in SINE B2 repeats

et al. 2022

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“…Metaplots, Aggregate Peak Analysis (APA), and Aggregate Domain Analysis (ADA) of these and other interactions were created using SIPMeta 29 . TAD identification, aggregate TAD analysis (ATA), and insulation scores were obtained from Genova 76 at 10 kb resolution.…”

Section: Methodsmentioning

confidence: 99%

Sex-specific multi-level 3D genome dynamics in the mouse brain

et al. 2022

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The female mammalian brain exhibits sex hormone-driven plasticity during the reproductive period. Recent evidence implicates chromatin dynamics in gene regulation underlying this plasticity. However, whether ovarian hormones impact higher-order chromatin organization in post-mitotic neurons in vivo is unknown. Here, we mapped the 3D genome of ventral hippocampal neurons across the oestrous cycle and by sex in mice. In females, we find cycle-driven dynamism in 3D chromatin organization, including in oestrogen response elements-enriched X chromosome compartments, autosomal CTCF loops, and enhancer-promoter interactions. With rising oestrogen levels, the female 3D genome becomes more similar to the male 3D genome. Cyclical enhancer-promoter interactions are partially associated with gene expression and enriched for brain disorder-relevant genes and pathways. Our study reveals unique 3D genome dynamics in the female brain relevant to female-specific gene regulation, neuroplasticity, and disease risk.

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“…CTCF annotation was generated by GENOVA 56 . Aggregate TAD analysis was performed using cooltools (v0.4.0) 57 .…”

Section: Hi-c Data Analysismentioning

confidence: 99%

Rad21 is the core subunit of the cohesin complex involved in directing genome organization

Sun

et al. 2021

Preprint

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The ring-shaped cohesin complex is an important factor regulating genome structure. It is thought to mediate the formation of chromatin loops and topologically associating domains (TADs) by loop extrusion. However, the regulation of association between cohesin and chromatin is poorly understood. In this study, we directly visualized cohesin loading after up-regulation of cohesin subunit Rad21 by identifying the formation of vermicelli-like structures via live cell super-resolution imaging. We also reveal that cohesin loading can be promoted by Rad21-loader interactions and accumulated contacts were shown at TAD corners while inter-TAD interactions increased after vermicelli formation, indicating that Rad21 is an important determinant of chromatin structure. Moreover, we find that cohesin saddle on topologically associating domains by FISH assay, which is consistent with the CTCF/cohesin-anchored chromatin loop model. Importantly, expression of Rad21 is strictly controlled, and aberrant expression of Rad21 leads to the formation of Rad21 “beads” in the nucleus. In summary, our observations provided important new biological insights into the mechanism of cohesin loading and its functions.

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Hi-C analyses with GENOVA: a case study with cohesin variants

Cited by 79 publications

References 59 publications

H3K9 trimethylation in active chromatin restricts the usage of functional CTCF sites in SINE B2 repeats

H3K9 trimethylation in active chromatin restricts the usage of functional CTCF sites in SINE B2 repeats

Sex-specific multi-level 3D genome dynamics in the mouse brain

Rad21 is the core subunit of the cohesin complex involved in directing genome organization

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