Exploring Epigenomic Datasets by ChIPseeker

Wang, Qianwen; Li, Ming; Wu, Tianzhi; Zhan, Li; Li, Lin; Chen, Meijun; Xie, Wenqin; Xie, Zijing; Hu, Erqiang; Xu, Shuaimei; Yu, Guangchuang

doi:10.1002/cpz1.585

Cited by 159 publications

(92 citation statements)

References 30 publications

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“…For SOX9 CUT&RUN peak calling, parameters —t input_file –p 1e-5 –f BAM –keep-dup all –n out_name was used to call narrow peaks. To check the SOX9 binding profile and enhancer activity of specific gene sets, proximal peaks (−2 kb to 2 kb relative to TSS) called by MACS2 were linked/annotated to genes by ChIPseeker version 1.34.1 ( 77 ). Then, computeMatrix and plotHeatmap functions from deepTools ( 78 ) were used to visualize peaks.…”

Section: Methodsmentioning

confidence: 99%

Aberrant cell state plasticity mediated by developmental reprogramming precedes colorectal cancer initiation

et al. 2023

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Cell state plasticity is carefully regulated in adult epithelia to prevent cancer. The aberrant expansion of the normally restricted capability for cell state plasticity in neoplasia is poorly defined. Using genetically engineered and carcinogen-induced mouse models of intestinal neoplasia, we observed that impaired differentiation is a conserved event preceding cancer development. Single-cell RNA sequencing (scRNA-seq) of premalignant lesions from mouse models and a patient with hereditary polyposis revealed that cancer initiates by adopting an aberrant transcriptional state characterized by regenerative activity, marked by Ly6a (Sca-1), and reactivation of fetal intestinal genes, including Tacstd2 (Trop2). Genetic inactivation of Sox9 prevented adenoma formation, obstructed the emergence of regenerative and fetal programs, and restored multilineage differentiation by scRNA-seq. Expanded chromatin accessibility at regeneration and fetal genes upon Apc inactivation was reduced by concomitant Sox9 suppression. These studies indicate that aberrant cell state plasticity mediated by unabated regenerative activity and developmental reprogramming precedes cancer development.

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Section: Methodsmentioning

confidence: 99%

Aberrant cell state plasticity mediated by developmental reprogramming precedes colorectal cancer initiation

et al. 2023

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“…Genomic coverage analysis and annotation of the synHEK3 reporters (Fig. 1D,E) were performed using the ChIPseeker package 79,80 in R. Enrichment of synHEK3 reporters across genomic features (Supplementary Fig. 1G,H) were performed using the annotatePeaks.pl function in Homer 81 .…”

Section: T7-assisted Reporter Mapping Library Processingmentioning

confidence: 99%

Chromatin context-dependent regulation and epigenetic manipulation of prime editing

Chen

Martin

et al. 2023

Preprint

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Prime editing is a powerful means of introducing precise changes to specific locations in mammalian genomes. However, the widely varying efficiency of prime editing across target sites of interest has limited its adoption in the context of both basic research and clinical settings. Here, we set out to exhaustively characterize the impact of the cis-chromatin environment on prime editing efficiency. Using a newly developed and highly sensitive method for mapping the genomic locations of a randomly integrated "sensor", we identify specific epigenetic features that strongly correlate with the highly variable efficiency of prime editing across different genomic locations. Next, to assess the interaction of trans-acting factors with the cis-chromatin environment, we develop and apply a pooled genetic screening approach with which the impact of knocking down various DNA repair factors on prime editing efficiency can be stratified by cis-chromatin context. Finally, we demonstrate that we can dramatically modulate the efficiency of prime editing through epigenome editing, i.e. altering chromatin state in a locus-specific manner in order to increase or decrease the efficiency of prime editing at a target site. Looking forward, we envision that the insights and tools described here will broaden the range of both basic research and therapeutic contexts in which prime editing is useful.

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“…For SOX9 CUT&RUN peak calling, parameters —t input_file –p 1e-5 –f BAM –keep-dup all –n out_name was used to call narrow peaks. To check the SOX9 binding profile and enhancer activity of specific gene sets, proximal peaks (-2kb to 2kb relative to TSS) called by macs2 were linked/annotated to genes by ChIPseeker version 1.34.1( 76 ). Then, computeMatrix and plotHeatmap functions from deepTools( 77 ) were used to visualize peaks.…”

Section: Methodsmentioning

confidence: 99%

Aberrant cell state plasticity mediated by developmental reprogramming precedes colorectal cancer initiation

Bala

Rennhack

Morris

et al. 2022

Preprint

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Cell state (phenotypic) plasticity is a carefully regulated feature of adult epithelial cells that enables adaptive responses to injury, inflammation, and other forms of stress. Aberrant expansion of the normally restricted capability for cell state plasticity to escape terminal differentiation is a critical aspect of neoplasia. The nongenetic factors and specific programs that mediate aberrant cell state plasticity and impaired differentiation require deeper characterization to understand this elusive aspect of cancer pathogenesis. Using genetically engineered and carcinogen-induced murine models of intestinal neoplasia, we demonstrate that impaired differentiation is a conserved event preceding cancer development. Single cell RNA-sequencing (scRNA-seq) of neoplastic intestinal lesions from both mouse models and a patient with familial adenomatous polyposis revealed that cancer initiates by adopting an aberrant transcriptional state characterized by nonoverlapping expression of a regenerative pathway, marked by Ly6a (Sca-1), and a fetal intestinal program, positive for Tacstd2 (Trop2). Genetic inactivation of Sox9 prevented adenoma formation in ApcKO mice, obstructed emergence of aberrant regenerative and fetal intestinal programs, and restored multi-lineage differentiation by scRNA-seq. Expanded chromatin accessibility at regeneration and fetal genes upon Apc inactivation was reduced by concomitant Sox9 suppression. These studies indicate that cancer initiation requires aberrant cell state plasticity mediated by unabated regenerative activity and developmental reprogramming.

show abstract

Exploring Epigenomic Datasets by ChIPseeker

Cited by 159 publications

References 30 publications

Aberrant cell state plasticity mediated by developmental reprogramming precedes colorectal cancer initiation

Aberrant cell state plasticity mediated by developmental reprogramming precedes colorectal cancer initiation

Chromatin context-dependent regulation and epigenetic manipulation of prime editing

Aberrant cell state plasticity mediated by developmental reprogramming precedes colorectal cancer initiation

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