scholarly journals Application of ATAC-Seq for genome-wide analysis of the chromatin state at single myofiber resolution

2021 ◽  
Author(s):  
Korin Sahinyan ◽  
Darren M Blackburn ◽  
Marie-Michelle Simon ◽  
Felicia Lazure ◽  
Tony Kwan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Wasting ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
The Body ◽  
Peak Calling ◽  
Genome Wide Analysis ◽  
Single Cell Sequencing ◽  
Genome Wide ◽  
Main Components

Skeletal myofibers are the main components of skeletal muscle which is the largest tissue in the body. Myofibers are highly adaptive in nature and they can vary in different biological and disease conditions. Therefore, transcriptional and epigenetic studies on myofibers are crucial to discover how chromatin alterations occur in the skeletal muscle under different conditions. However, due to the heterogenous nature of skeletal muscle, studying myofibers in isolation proves to be a challenging task. Single cell sequencing has permitted for the study of the epigenome of isolated myonuclei. While this provides sequencing with high dimensionality, the sequencing depth is lacking, which makes comparisons between different biological conditions difficult. Here we report the first implementation of single myofiber ATAC-Seq, which permits for the sequencing of an individual myofiber at a depth sufficient for peak calling and for comparative analysis of chromatin accessibility under various physiological, physical and disease conditions. Application of this technique revealed significant differences in chromatin accessibility between resting and regenerating myofibers. This technique can lead to wide application in identifying chromatin regulatory elements and epigenetic mechanisms in muscle fibers during development and in muscle-wasting diseases.

scholarly journals Mitochondrial Dysfunction Is a Common Denominator Linking Skeletal Muscle Wasting Due to Disease, Aging, and Prolonged Inactivity

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 588
Author(s):  
Hayden W. Hyatt ◽  
Scott K. Powers
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Chronic Diseases ◽  
Muscle Mass ◽  
Cancer Chemotherapy ◽  
Muscle Wasting ◽  
The Body ◽  
Common Denominator ◽  
Skeletal Muscle Wasting ◽  
Vital Functions

Skeletal muscle is the most abundant tissue in the body and is required for numerous vital functions, including breathing and locomotion. Notably, deterioration of skeletal muscle mass is also highly correlated to mortality in patients suffering from chronic diseases (e.g., cancer). Numerous conditions can promote skeletal muscle wasting, including several chronic diseases, cancer chemotherapy, aging, and prolonged inactivity. Although the mechanisms responsible for this loss of muscle mass is multifactorial, mitochondrial dysfunction is predicted to be a major contributor to muscle wasting in various conditions. This systematic review will highlight the biochemical pathways that have been shown to link mitochondrial dysfunction to skeletal muscle wasting. Importantly, we will discuss the experimental evidence that connects mitochondrial dysfunction to muscle wasting in specific diseases (i.e., cancer and sepsis), aging, cancer chemotherapy, and prolonged muscle inactivity (e.g., limb immobilization). Finally, in hopes of stimulating future research, we conclude with a discussion of important future directions for research in the field of muscle wasting.

scholarly journals The Integrity of piRNA Clusters is Abolished by Insulators in the Drosophila Germline

Genes ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 209 ◽  
Author(s):  
Elizaveta Radion ◽  
Olesya Sokolova ◽  
Sergei Ryazansky ◽  
Pavel Komarov ◽  
Yuri Abramov ◽  
...  
Keyword(s):  
Binding Sites ◽  
Regulatory Elements ◽  
Evolutionary Constraints ◽  
Heterochromatin Protein 1 ◽  
Heterochromatin Protein ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
Pirna Cluster ◽  
A Genome ◽  
Cluster Activity

Piwi-interacting RNAs (piRNAs) control transposable element (TE) activity in the germline. piRNAs are produced from single-stranded precursors transcribed from distinct genomic loci, enriched by TE fragments and termed piRNA clusters. The specific chromatin organization and transcriptional regulation of Drosophila germline-specific piRNA clusters ensure transcription and processing of piRNA precursors. TEs harbour various regulatory elements that could affect piRNA cluster integrity. One of such elements is the suppressor-of-hairy-wing (Su(Hw))-mediated insulator, which is harboured in the retrotransposon gypsy. To understand how insulators contribute to piRNA cluster activity, we studied the effects of transgenes containing gypsy insulators on local organization of endogenous piRNA clusters. We show that transgene insertions interfere with piRNA precursor transcription, small RNA production and the formation of piRNA cluster-specific chromatin, a hallmark of which is Rhino, the germline homolog of the heterochromatin protein 1 (HP1). The mutations of Su(Hw) restored the integrity of piRNA clusters in transgenic strains. Surprisingly, Su(Hw) depletion enhanced the production of piRNAs by the domesticated telomeric retrotransposon TART, indicating that Su(Hw)-dependent elements protect TART transcripts from piRNA processing machinery in telomeres. A genome-wide analysis revealed that Su(Hw)-binding sites are depleted in endogenous germline piRNA clusters, suggesting that their functional integrity is under strict evolutionary constraints.

scholarly journals Genome-Wide Analysis Reveals Extensive Changes in LncRNAs during Skeletal Muscle Development in Hu Sheep

Genes ◽  
2017 ◽  
Vol 8 (8) ◽  
pp. 191 ◽  
Author(s):  
Caifang Ren ◽  
Mingtian Deng ◽  
Yixuan Fan ◽  
Hua Yang ◽  
Guomin Zhang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Skeletal Muscle Development ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
Hu Sheep

scholarly journals A genome-wide analysis of open chromatin in human tracheal epithelial cells reveals novel candidate regulatory elements for lung function

Thorax ◽  
2011 ◽  
Vol 67 (5) ◽  
pp. 385-391 ◽  
Author(s):  
Jared M Bischof ◽  
Christopher J Ott ◽  
Shih-Hsing Leir ◽  
Nehal Gosalia ◽  
Lingyun Song ◽  
...  
Keyword(s):  
Lung Function ◽  
Epithelial Cells ◽  
Regulatory Elements ◽  
Open Chromatin ◽  
Genome Wide Analysis ◽  
Tracheal Epithelial Cells ◽  
Genome Wide ◽  
A Genome ◽  
Tracheal Epithelial

scholarly journals Single-cell ATAC-seq Signal Extraction and Enhancement with SCATE

2019 ◽  
Author(s):  
Zhicheng Ji ◽  
Weiqiang Zhou ◽  
Hongkai Ji
Keyword(s):  
Single Cell ◽  
State Of The Art ◽  
Single Cells ◽  
Regulatory Elements ◽  
Single Cell Sequencing ◽  
Statistical Framework ◽  
Genome Wide ◽  
Cell Subpopulations ◽  
Accessible Chromatin ◽  
Regulatory Landscape

AbstractSingle-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) is the state-of-the-art technology for analyzing genome-wide regulatory landscape in single cells. Single-cell ATAC-seq data are sparse and noisy. Analyzing such data is challenging. Existing computational methods cannot accurately reconstruct activities of individual cis-regulatory elements (CREs) in individual cells or rare cell subpopulations. We present a new statistical framework, SCATE, that adaptively integrates information from co-activated CREs, similar cells, and publicly available regulome data to substantially increase the accuracy for estimating activities of individual CREs. We show that using SCATE, one can better reconstruct the regulatory landscape of a heterogeneous sample.

scholarly journals Single-Cell Epigenomics and Functional Fine-Mapping of Atherosclerosis GWAS Loci

2021 ◽  
Author(s):  
Tiit Örd ◽  
Kadri Õunap ◽  
Lindsey Stolze ◽  
Rédouane Aherrahrou ◽  
Valtteri Nurminen ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cell Types ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Cell Type ◽  
Atherosclerotic Lesions ◽  
Genome Wide ◽  
Single Nucleus

Rationale: Genome-wide association studies (GWAS) have identified hundreds of loci associated with coronary artery disease (CAD). Many of these loci are enriched in cis-regulatory elements (CREs) but not linked to cardiometabolic risk factors nor to candidate causal genes, complicating their functional interpretation. Objective: Single nucleus chromatin accessibility profiling of the human atherosclerotic lesions was used to investigate cell type-specific patterns of CREs, to understand transcription factors establishing cell identity and to interpret CAD-relevant, non-coding genetic variation. Methods and Results: We used single nucleus ATAC-seq to generate DNA accessibility maps in > 7,000 cells derived from human atherosclerotic lesions. We identified five major lesional cell types including endothelial cells, smooth muscle cells, monocyte/macrophages, NK/T-cells and B-cells and further investigated subtype characteristics of macrophages and smooth muscle cells transitioning into fibromyocytes. We demonstrated that CAD associated genetic variants are particularly enriched in endothelial and smooth muscle cell-specific open chromatin. Using single cell co-accessibility and cis-eQTL information, we prioritized putative target genes and candidate regulatory elements for ~30% of all known CAD loci. Finally, we performed genome-wide experimental fine-mapping of the CAD GWAS variants using epigenetic QTL analysis in primary human aortic endothelial cells and STARR-Seq massively parallel reporter assay in smooth muscle cells. This analysis identified potential causal SNP(s) and the associated target gene for over 30 CAD loci. We present several examples where the chromatin accessibility and gene expression could be assigned to one cell type predicting the cell type of action for CAD loci. Conclusions: These findings highlight the potential of applying snATAC-seq to human tissues in revealing relative contributions of distinct cell types to diseases and in identifying genes likely to be influenced by non-coding GWAS variants.

scholarly journals Integrative analysis of epigenetics data identifies gene-specific regulatory elements

2019 ◽  
Author(s):  
Florian Schmidt ◽  
Alexander Marx ◽  
Marie Hebel ◽  
Martin Wegner ◽  
Nina Baumgarten ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Cell Types ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Genome Wide ◽  
A Genome ◽  
Gene Level ◽  
Regulatory Landscape ◽  
Regulatory Sites ◽  
Validation Experiments

AbstractUnderstanding the complexity of transcriptional regulation is a major goal of computational biology. Because experimental linkage of regulatory sites to genes is challenging, computational methods considering epigenomics data have been proposed to create tissue-specific regulatory maps. However, we showed that these approaches are not well suited to account for the variations of the regulatory landscape between cell-types. To overcome these drawbacks, we developed a new method called STITCHIT, that identifies and links putative regulatory sites to genes. Within STITCHIT, we consider the chromatin accessibility signal of all samples jointly to identify regions exhibiting a signal variation related to the expression of a distinct gene. STITCHIToutperforms previous approaches in various validation experiments and was used with a genome-wide CRISPR-Cas9 screen to prioritize novel doxorubicin-resistance genes and their associated non-coding regulatory regions. We believe that our work paves the way for a more refined understanding of transcriptional regulation at the gene-level.

scholarly journals Chromatin accessibility landscape and regulatory network of high-altitude hypoxia adaptation

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jingxue Xin ◽  
Hui Zhang ◽  
Yaoxi He ◽  
Zhana Duren ◽  
Caijuan Bai ◽  
...  
Keyword(s):  
High Altitude ◽  
Regulatory Network ◽  
Cell Types ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Remarkable Case ◽  
Genome Wide ◽  
Altitude Adaptation ◽  
Time Courses ◽  
Coding Variants

Abstract High-altitude adaptation of Tibetans represents a remarkable case of natural selection during recent human evolution. Previous genome-wide scans found many non-coding variants under selection, suggesting a pressing need to understand the functional role of non-coding regulatory elements (REs). Here, we generate time courses of paired ATAC-seq and RNA-seq data on cultured HUVECs under hypoxic and normoxic conditions. We further develop a variant interpretation methodology (vPECA) to identify active selected REs (ASREs) and associated regulatory network. We discover three causal SNPs of EPAS1, the key adaptive gene for Tibetans. These SNPs decrease the accessibility of ASREs with weakened binding strength of relevant TFs, and cooperatively down-regulate EPAS1 expression. We further construct the downstream network of EPAS1, elucidating its roles in hypoxic response and angiogenesis. Collectively, we provide a systematic approach to interpret phenotype-associated noncoding variants in proper cell types and relevant dynamic conditions, to model their impact on gene regulation.

ATAC-pipe: general analysis of genome-wide chromatin accessibility

2019 ◽  
Vol 20 (5) ◽  
pp. 1934-1943 ◽  
Author(s):  
Zuqi Zuo ◽  
Yonghao Jin ◽  
Wen Zhang ◽  
Yichen Lu ◽  
Bin Li ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Length Distribution ◽  
Original Data ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
General Analysis ◽  
Read Length ◽  
Genome Wide ◽  
Cell Type Specific

Abstract Assay of Transposase-Accessible Chromatin by deep sequencing (ATAC-seq) has been widely used to profile the chromatin accessibility genome-wide. For the absence of an integrated scheme for deep data mining of specific biological issues, here we present ATAC-pipe, an efficient pipeline for general analysis of chromatin accessibility data obtained from ATAC-seq experiments. ATAC-pipe captures information includes not only the quality of original data and genome-wide chromatin accessibility but also signatures of significant differential peaks, transcription factor (TF) occupancy and nucleosome positions around regulatory sites. In addition, ATAC-pipe automatically converts statistic results into intuitive plots at publication quality, such as the read length distribution, heatmaps of sample clustering and cell-type-specific regulatory elements, enriched TF occupancy with motifs footprints and TF-driven regulatory networks. ATAC-pipe provides convenient workflow for researchers to study chromatin accessibility and gene regulation. Availability https://github.com/QuKunLab/ATAC-pipe

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