peakC: a flexible, non-parametric peak calling package for 4C and Capture-C data

Geeven, Geert; Teunissen, Hans; Laat, Wouter de; Wit, Elzo de

doi:10.1093/nar/gky443

Cited by 69 publications

(67 citation statements)

References 36 publications

(55 reference statements)

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“…We generated 4C data for untreated and 24h IAA treated Wapl-AID and Rad21-AID cells. 4C was performed as previously described (Geeven et al, 2018;van de Werken et al, 2012) using a two-step PCR method for indexing described first in (Haarhuis et al, 2017). We used MboI as the first restriction enzyme and Csp6I as the second restriction fragment.…”

Section: C-seqmentioning

confidence: 99%

WAPL maintains dynamic cohesin to preserve lineage specific distal gene regulation

Liu

Maresca

Brand

et al. 2019

Preprint

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HIGHLIGHTS 1. The cohesin release factor WAPL is crucial for maintaining a pluripotency-specific phenotype.2. Dynamic cohesin is enriched at lineage specific loci and overlaps with binding sites of pluripotency transcription factors.3. Expression of lineage specific genes is maintained by dynamic cohesin binding through the formation of promoter-enhancer associated self-interaction domains.4. CTCF-independent cohesin binding to chromatin is controlled by the pioneer factor OCT4. SUMMARYThe cohesin complex plays essential roles in sister chromatin cohesin, chromosome organization and gene expression. The role of cohesin in gene regulation is incompletely understood. Here, we report that the cohesin release factor WAPL is crucial for maintaining a pool of dynamic cohesin bound to regions that are associated with lineage specific genes in mouse embryonic stem cells. These regulatory regions are enriched for active enhancer marks and transcription factor binding sites, but largely devoid of CTCF binding sites. Stabilization of cohesin, which leads to a loss of dynamic cohesin from these regions, does not affect transcription factor binding or active enhancer marks, but does result in changes in promoter-enhancer interactions and downregulation of genes.Acute cohesin depletion can phenocopy the effect of WAPL depletion, showing that cohesin plays a crucial role in maintaining expression of lineage specific genes. The binding of dynamic cohesin to chromatin is dependent on the pluripotency transcription factor OCT4, but not NANOG. Finally, dynamic cohesin binding sites are also found in differentiated cells, suggesting that they represent a general regulatory principle. We propose that cohesin dynamically binding to regulatory sites creates a favorable spatial environment in which promoters and enhancers can communicate to ensure proper gene expression.

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Section: C-seqmentioning

confidence: 99%

WAPL maintains dynamic cohesin to preserve lineage specific distal gene regulation

Liu

Maresca

Brand

et al. 2019

Preprint

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“…We recently presented a non-parametric regression-based analysis tool, called peakC, for reproducible calling of chromatin interaction peaks from 4C and Capture-C datasets (Geeven et al, 2018). To create peakHiC, we modified this peak caller for systematic chromatin loop identification from our Hi-C derived V4C contact profiles (See Figure 1C).…”

Section: Chromatin Loop Identification By Peakhicmentioning

confidence: 99%

“…For human heart Hi-C from left atrium (LA) and left ventricle (LV), we used the data from 4 independent Hi-C templates from different donors described in this manuscript. We adapted peakC (Geeven et al, 2018) to identify peaks in Hi-C data using the replicate V4C profiles in these 3 different Hi-C datasets. peakC is a robust non-parametric method developed initially for the identification of contact peaks in 4C-Seq and Capture-C data.…”

Section: Peakhic: Peak Calling -First Roundmentioning

confidence: 99%

Detailed Regulatory Interaction Map of the Human Heart Facilitates Gene Discovery for Cardiovascular Disease

Bianchi

Geeven

Tucker

et al. 2019

Preprint

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SummaryMost disease-associated variants identified by population based genetic studies are non-coding, which compromises finding causative genes and mechanisms. Presumably they interact through looping with nearby genes to modulate transcription. Hi-C provides the most complete and unbiased method for genome-wide identification of potential regulatory interactions, but finding chromatin loops in Hi-C data remains difficult and tissue specific data are limited. We have generated Hi-C data from primary cardiac tissue and developed a method, peakHiC, for sensitive and quantitative loop calling to uncover the human heart regulatory interactome. We identify complex CTCF-dependent and -independent contact networks, with loops between coding and non-coding gene promoters, shared enhancers and repressive sites. Across the genome, enhancer interaction strength correlates with gene transcriptional output and loop dynamics follows CTCF, cohesin and H3K27Ac occupancy levels. Finally, we demonstrate that intersection of the human heart regulatory interactome with cardiovascular disease variants facilitates prioritizing disease-causative genes.

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“…To estimate the genomic range of the near-cis interactions we used 4C-ker (Raviram et al, 2016). The read counts were analyzed using the R package PeakC (Geeven et al, 2018) with a flanking window size of 700kb around the viewpoint, a running window size of 10 and false-discovery ratio threshold of 0.01. The definition of genomic regions was done using the UCSC Genome Browser (Kent et al, 2002) and ENCODE annotation data (Rosenbloom et al, 2013).…”

Section: Chromosome Conformation Capture (4c)mentioning

confidence: 99%

“…c) Relative expression of CCND1 in scrambled, ESPL1 and TOP2A. d) Interactions of the CCND1 promoter with surrounding regions identified by read counts calculated byPeakC(Geeven et al, 2018) for MCF10A, MCF10CA, scrambled, ESPL1, and TOP2A. Interactions that are common for more than one condition are boxed-in in black.…”

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confidence: 99%

Induced aneuploidy disrupts MCF10A acini formation and CCND1 expression

Waschow

Wang

Saary

et al. 2019

Preprint

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Abnormal karyotypes, namely aneuploidy, can be detected in nearly all cancer entities at different grades. The impact of these altering mutations on epigenetic regulation, especially on promoterenhancer interactions are not well understood. Here, we applied a 3D model of MCF10A cells in a high-content screen to measure induced aneuploidy by RNA interference of 82 mitotic genes associated with aneuploidy and breast cancer. Perturbation of ESPL1 and TOP2A expression led to increased mitotic instability and subsequent aneuploidy and polylobed nuclei. During acinus formation these polylobed cells disrupted proper acinus rotation inhibiting the development of a hollow lumen and a polarized outer cell layer. Further, gene expression profiling identified upregulated CCND1 among other breast cancer related genes. We show that acquisition of aneuploidy affects the morphogenesis of MCF10A acini and expression of cancer relevant genes.By conducting 4C chromosome capturing experiments we linked the alteration of interactions of the promoter region to CCND1 upregulation.

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peakC: a flexible, non-parametric peak calling package for 4C and Capture-C data

Cited by 69 publications

References 36 publications

WAPL maintains dynamic cohesin to preserve lineage specific distal gene regulation

WAPL maintains dynamic cohesin to preserve lineage specific distal gene regulation

Detailed Regulatory Interaction Map of the Human Heart Facilitates Gene Discovery for Cardiovascular Disease

Induced aneuploidy disrupts MCF10A acini formation and CCND1 expression

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