An ATAC-seq atlas of chromatin accessibility in mouse tissues

Liu, Chuanyu; Wang, Mingyue; Wei, Xiaoyü; Wu, Liang; Xu, Jiangshan; Dai, Xi; Xia, Jun; Cheng, Mengnan; Yuan, Yue; Zhang, Pengfan; Li, Ji‐Guang; Feng, Taiqing; Chen, Ao; Zhang, Wenwei; Chen, Fang; Shang, Zhouchun; Zhang, Xiuqing; Peters, Brock A.; Liu, Longqi

doi:10.1038/s41597-019-0071-0

Cited by 101 publications

(126 citation statements)

References 42 publications

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“…Changes in chromatin conformation and accessibility are widespread during development where cells undergoing differentiation exhibit major alterations in gene expression [1]. Consistent with this, comparison of chromatin differences between cell types by ATAC-seq has identified large numbers of regions of differing accessibility [28], supporting previous findings ,using the similar DNase I sensitivity assay, that chromatin accessibility at expression quantitative trait loci (eQTLs) is the major determinant of human expression variation [29]. Many such accessible regions overlap with enhancer modifications confirming the cell type specific regulation of gene expression by enhancers.…”

Section: Discussionmentioning

confidence: 71%

Dynamic chromatin accessibility landscape changes following interleukin-1 stimulation

Barter

Cheung

Falk

et al. 2020

Preprint

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Genome-wide methods for examining chromatin modification provide detailed information on regulatory regions of the genome. Dynamic modifications of chromatin allow rapid access of the gene regulatory machinery to condensed genomic regions facilitating subsequent gene expression. Inflammatory cytokine stimulation of cells can cause rapid gene expression changes through direct signalling pathway-mediated transcription factor activation and regulatory element binding.Here we used the Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq) to assess regions of the genome that are differentially accessible following treatment of cells with interleukin-1 (IL-1). We identified 126,483 open chromatin regions, with 241 regions significantly differentially accessible following stimulation, with 64 and 177 more or less accessible, respectively. These differentially accessible regions predominantly correspond to regions of the genome marked as enhancers. Motif searching identified an overrepresentation of a number of transcription factors, most notably RelA in the regions becoming more accessible, with analysis of ChIP-seq data confirmed RelA binding to these regions. A significant correlation in differential chromatin accessibility and gene expression was also observed.Functionality in regulating gene expression was confirmed using CRISPR/Cas9 genome-editing to delete regions for that became more accessible following stimulation in the genes MMP13, IKBKE and C1QTNF1. These same regions were also accessible for activation using a dCas9-transcriptional activator and showed enhancer activity in a cellular model.Together, these data describe and functionally validate a number of dynamically accessible chromatin regions involved in inflammatory signalling.

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Section: Discussionmentioning

confidence: 71%

Dynamic chromatin accessibility landscape changes following interleukin-1 stimulation

Barter

Cheung

Falk

et al. 2020

Preprint

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“…Since ChIP-seq experiments showed a correlation between the strength of transcription and H2A.Z enrichment at the TSS, we can conclude that in muscle cells, as in any cell type, a correlation exists between transcription strength and chromatin accessibility. ChIP-seq and ATAC-seq alignment further indicated that in muscle fibers, as in other mouse tissues 32 , chromatin was the most accessible between the +1 and the -1 nucleosomes surrounding the TSS (Fig. 2D).…”

Section: Invalidation Of H2az-1 and H2az-2 Inmentioning

confidence: 80%

H2A.Z is dispensable for both basal and activated transcription in post-mitotic mouse muscles

Belotti

Lacoste

Simonet

et al. 2019

Preprint

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ABSTRACTThe histone variant H2A.Z is enriched in nucleosomes surrounding the transcription start site of active promoters, suggesting that it might be implicated in transcription. It is also required during mitosis. However, evidences obtained so far mainly rely on correlative evidences obtained in actively dividing cells. We have defined a paradigm in which cell cycle cannot interfere with H2A.Z transcriptional studies by developing an in vivo systems to invalidate H2A.Z in terminally differentiated post-mitotic muscle cells to dissociate its role during transcription from its role during mitosis. ChIP-seq, RNA-seq and ATAC-seq experiments performed on H2A.Z KO post-mitotic muscle cells show that this histone variant is neither required to maintain nor to activate transcription. Altogether, this study provides in vivo evidence that in the absence of mitosis H2A.Z is dispensable for transcription and that the enrichment of H2A.Z on active promoters is rather a marker than an actor of transcriptional activity.

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“…The ATAC-seq data were processed (trim, alignment, filter, and QC) using the ATAC-seq pipeline from the Kundaje lab 31,32 (Table 2). The model-based analysis of ChIP-seq (MACS2) 33 version 2.1.2 was used to identify the peak regions with options −B, −q 0.01 -- nomodel, −f BAM, −g mm.…”

Section: Methodsmentioning

confidence: 99%

An ATAC-seq atlas of chromatin accessibility in mouse tissues

Liu

Wang

Wei

et al. 2019

Preprint

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17The Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) is a 18 fundamental epigenomics approach and has been widely used in profiling the chromatin 19 accessibility dynamics in multiple species. A comprehensive reference of ATAC-seq datasets 20 for mammalian tissues is important for the understanding of regulatory specificity and 21 developmental abnormality caused by genetic or environmental alterations. Here, we report 22 an adult mouse ATAC-seq atlas by producing a total of 66 ATAC-seq profiles from 20 primary 23 tissues of both male and female mice. The ATAC-seq read enrichment, fragment size 24 distribution, and reproducibility between replicates demonstrated the high quality of the full 25 dataset. We identified a total of 296,574 accessible elements, of which 26,916 showed tissue-26 specific accessibility. Further, we identified key transcription factors specific to distinct tissues 27 and found that the enrichment of each motif reflects the developmental similarities across 28 tissues. In summary, our study provides an important resource on the mouse epigenome and 29 2 will be of great importance to various scientific disciplines such as development, cell 30 reprogramming, and genetic disease. 32Background & Summary 33Although most of the protein-coding genes in human and model animals such as mouse have 34 been extensively annotated, vast regions of the genome are noncoding sequences (e.g., 35roughly 98% of the human genome) and still poorly understood 1,2 . During the last decade, the 36 development of next-generation sequencing (NGS) based epigenomics techniques (e.g., ChIP-37 seq and DNase-seq) have significantly facilitated the identification of functional genomic 38 regions 3 . For example, by comparing the histone modifications and transcription factor (TF) 39 binding patterns throughout the mouse genome in a wide spectrum of tissues and cell types, 40 Yue et al. 4,5 have made significant progress towards a comprehensive catalog of potential 41 functional elements in the mouse genome. So far, the international human epigenome 42 consortium (IHEC), including ENCODE and the NIH Roadmap epigenomics projects, have 43 profiled thousands of epigenomes including DNA methylation, genome-wide binding of TFs, 44 histone modifications, and chromatin accessibility. This has resulted in the discovery of over 45 5 million cis-regulatory elements (CREs) in the human genome 6-8 . These data resources have 46 created an important baseline for further study of diverse biological processes, such as 47 development, cell reprogramming, and human disease 9-13 . 48 49 The accessibility of CREs, which is important for switching on and off gene expression 14 , 50 is strongly associated with transcriptional activity. To date, detection of DNase I hypersensitive 51 sites (DHSs) within chromatin by DNase-seq has been extensively used to map accessible 52 genomic regions in diverse organisms including the laboratory mouse 5 . In 2013, Buenrostro et 53 al. 15 reported an alternative approach, termed ATAC...

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An ATAC-seq atlas of chromatin accessibility in mouse tissues

Cited by 101 publications

References 42 publications

Dynamic chromatin accessibility landscape changes following interleukin-1 stimulation

Dynamic chromatin accessibility landscape changes following interleukin-1 stimulation

H2A.Z is dispensable for both basal and activated transcription in post-mitotic mouse muscles

An ATAC-seq atlas of chromatin accessibility in mouse tissues

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