ChIPseeker: an R/Bioconductor package for ChIP peak annotation, comparison and visualization

Yu, Guangchuang; Wang, Li Gen; He, Qing-Yu

doi:10.1093/bioinformatics/btv145

Cited by 2,949 publications

(2,265 citation statements)

References 11 publications

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“…MORC3 ChIPseq peaks were identified with MACS version 2.1.0 (34). Defined MORC3 peaks were then annotated to the mm9 genome with the ChIPseeker R package (35). For H3K4me1 (GSM769009), H3K9me3 (GSM1000147), H3K27me3 (GSM1000089), H3K27ac (GSM1000099), H3K4me3 (GSM769008), H3K9ac (GSM1000127), p300(GSM918750), and RNA polymerase II (GSM723019) ChIPseq, data raw sequencing data were downloaded from ENCODE and processed as described above.…”

Section: Methodsmentioning

confidence: 99%

Mouse MORC3 is a GHKL ATPase that localizes to H3K4me3 marked chromatin

Yen

Pastor

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Microrchidia (MORC) proteins are GHKL (gyrase, heat-shock protein 90, histidine kinase, MutL) ATPases that function in gene regulation in multiple organisms. Animal MORCs also contain CW-type zinc finger domains, which are known to bind to modified histones. We solved the crystal structure of the murine MORC3 ATPase-CW domain bound to the nucleotide analog AMPPNP (phosphoaminophosphonic acidadenylate ester) and in complex with a trimethylated histone H3 lysine 4 (H3K4) peptide (H3K4me3). We observed that the MORC3 N-terminal ATPase domain forms a dimer when bound to AMPPNP. We used native mass spectrometry to show that dimerization is ATPdependent, and that dimer formation is enhanced in the presence of nonhydrolyzable ATP analogs. The CW domain uses an aromatic cage to bind trimethylated Lys4 and forms extensive hydrogen bonds with the H3 tail. We found that MORC3 localizes to promoters marked by H3K4me3 throughout the genome, consistent with its binding to H3K4me3 in vitro. Our work sheds light on aspects of the molecular dynamics and function of MORC3.X-ray crystallography | histone mark reader | ATPase | native mass spectrometry T he Microrchidia (MORC) family of ATPase proteins has been shown to be an important regulator of gene silencing in multiple organisms. This family was first described in mice, when it was discovered that morc1 null males showed arrested spermatogenesis (1). This arrest was later shown to be associated with transposon derepression, implicating murine MORC1 as a crucial mediator of transposon silencing (2). Arabidopsis thaliana MORC1 and MORC6 were shown to mediate silencing of transposons in a manner largely independent of changes in DNA methylation (3)(4)(5). Studies in Caenorhabditis elegans, which lack DNA methylation, also concluded that the single MORC gene in this organism plays a role in transgene silencing (4). Although the biological importance of MORC ATPases in enforcing gene silencing across multiple organisms is clear, how they are targeted and how they function are poorly understood.The MORC ATPases share a similar domain arrangement. The N terminus contains a GHKL (gyrase, heat-shock protein 90, histidine kinase, MutL) type ATPase domain, and at the C terminus is a coiled-coil segment. MORCs have been reported to form functional homomultimers or heteromultimers, where multimerization is likely mediated by the N-and/or the C-terminal domains (4, 6, 7). The coiled-coil region has been proposed to promote constitutive dimerization, whereas N-terminal ATPase head dimerization occurs only on ATP binding (6). This is consistent with other GHKL ATPases described in the literature, many of which have been reported to undergo ATP-dependent dimerization (8-10). Both plant and animal MORCs are capable of forming nuclear bodies, and mutations that impair ATP binding and/or hydrolysis disrupt nuclear body formation of human MORC3 (6).Animal MORCs also carry a CW-type zinc finger domain, which has been proposed to read histone H3 lysine 4 (H3K4) dimethylation and trimethylation mark...

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Section: Methodsmentioning

confidence: 99%

Mouse MORC3 is a GHKL ATPase that localizes to H3K4me3 marked chromatin

Yen

Pastor

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Using an R implementation, the consistency of replicated sample peaks was assessed with the Irreproducible Discovery Rate algorithm (46). Differential binding analysis was performed using an R Bioconductor package DBChIP (47) and annotated using ChIPseeker (48). To facilitate comparisons with ChIP-seq data we hope to generate in the future using patient derived airway epithelial cells, only autosomal binding regions were used to define differential binding and subsequent analysis.…”

Section: Methodsmentioning

confidence: 99%

Cistrome-based Cooperation between Airway Epithelial Glucocorticoid Receptor and NF-κB Orchestrates Anti-inflammatory Effects

Kadiyala

Sasse

Altonsy

et al. 2016

Journal of Biological Chemistry

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Antagonism of pro-inflammatory transcription factors by monomeric glucocorticoid receptor (GR) has long been viewed as central to glucocorticoid (GC) efficacy. However, the mechanisms and targets through which GCs exert therapeutic effects in diseases such as asthma remain incompletely understood. We previously defined a surprising cooperative interaction between GR and NF-B that enhanced expression of A20 (TNFAIP3), a potent inhibitor of NF-B. Here we extend this observation to establish that A20 is required for maximal cytokine repression by GCs. To ascertain the global extent of GR and NF-B cooperation, we determined genome-wide occupancy of GR, the p65 subunit of NF-B, and RNA polymerase II in airway epithelial cells treated with dexamethasone, TNF, or both using chromatin immunoprecipitation followed by deep sequencing. We found that GR recruits p65 to dimeric GR binding sites across the genome and discovered additional regulatory elements in which GR-p65 cooperation augments gene expression. GR targets regulated by this mechanism include key anti-inflammatory and injury response genes such as SERPINA1, which encodes ␣1 antitrypsin, and FOXP4, an inhibitor of mucus production. Although dexamethasone treatment reduced RNA polymerase II occupancy of TNF targets such as IL8 and TNFAIP2, we were unable to correlate specific binding sequences for GR or occupancy patterns with repressive effects on transcription. Our results suggest that cooperative anti-inflammatory gene regulation by GR and p65 contributes to GC efficacy, whereas tethering interactions between GR and p65 are not universally required for GC-based gene repression.

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“…The R/Bioconductor package ChIPseeker (v1.13.1) (YU et al 2015) was used to first annotate the QTL locations to the nearest annotated gene in the UCSC R/Bioconductor package TxDb.Mmusculus.UCSC.mm10.knownGene (v3.4.0) (LAWRENCE et al 2013) using the function annotatePeak with options tssRegion = c(-1, 1), TxDb = TxDb.Mmusculus.UCSC.mm10.knownGene, annoDb = "org.Mm.eg.db", overlap = "all", and all other options set to default. Then, the syntenic regions in human (hg19) to each of the nearest QTL genes were mapped using the R/Bioconductor package biomaRt (v2.33.4) (DURINCK et al 2009).…”

Section: Identification Of Human Loci Syntenic To Mouse Qtl and Intementioning

confidence: 99%

Genetic Drivers of Pancreatic Islet Function

et al. 2018

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The majority of gene loci that have been associated with type 2 diabetes play a role in pancreatic islet function. To evaluate the role of islet gene expression in the etiology of diabetes, we sensitized a genetically diverse mouse population with a Western diet high in fat (45%-kcal) and sucrose (34%) and carried out genome-wide association mapping of diabetes-related phenotypes. We quantified mRNA abundance in the islets and identified 18,820 expression quantitative trait loci. We applied mediation analysis to identify candidate causal driver genes at loci that affect the abundance of numerous transcripts. These include two genes previously associated with monogenic diabetes (PDX1 and HNF4A), as well as three genes with nominal association with diabetes-related traits in humans (FAM83E, IL6ST, and SAT2). We grouped transcripts into gene modules and mapped regulatory loci for modules enriched with transcripts specific for α-cells, and another specific for δ-cells. However, no single module enriched for β-cell-specific transcripts, suggesting heterogeneity of gene expression patterns within the β-cell population. A module enriched in transcripts associated with branched chain amino acid metabolism was the most strongly correlated with physiological traits that reflect insulin resistance. Although the mice in this study were not overtly diabetic, the analysis of pancreatic islet gene expression under dietary-induced stress enabled us to identify correlated variation in groups of genes that are functionally linked to diabetes-associated physiological traits. Our analysis suggests an expected degree of concordance between diabetes-associated loci in the mouse with those found in human populations and demonstrates how the mouse can provide evidence to support nominal associations found in human genome-wide association mapping.4

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ChIPseeker: an R/Bioconductor package for ChIP peak annotation, comparison and visualization

Abstract: ChIPseeker is released under Artistic-2.0 License. The source code and documents are freely available through Bioconductor (http://www.bioconductor.org/packages/release/bioc/html/ChIPseeker.html).

Cited by 2,949 publications

References 11 publications

Mouse MORC3 is a GHKL ATPase that localizes to H3K4me3 marked chromatin

Mouse MORC3 is a GHKL ATPase that localizes to H3K4me3 marked chromatin

Cistrome-based Cooperation between Airway Epithelial Glucocorticoid Receptor and NF-κB Orchestrates Anti-inflammatory Effects

Genetic Drivers of Pancreatic Islet Function

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