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https://www.readbyqxmd.com/read/29342231/mapping-gene-regulatory-networks-from-single-cell-omics-data
#1
Mark W E J Fiers, Liesbeth Minnoye, Sara Aibar, Carmen Bravo González-Blas, Zeynep Kalender Atak, Stein Aerts
Single-cell techniques are advancing rapidly and are yielding unprecedented insight into cellular heterogeneity. Mapping the gene regulatory networks (GRNs) underlying cell states provides attractive opportunities to mechanistically understand this heterogeneity. In this review, we discuss recently emerging methods to map GRNs from single-cell transcriptomics data, tackling the challenge of increased noise levels and data sparsity compared with bulk data, alongside increasing data volumes. Next, we discuss how new techniques for single-cell epigenomics, such as single-cell ATAC-seq and single-cell DNA methylation profiling, can be used to decipher gene regulatory programmes...
January 12, 2018: Briefings in Functional Genomics
https://www.readbyqxmd.com/read/29296732/chromatin-dynamics-during-the-differentiation-of-long-term-hematopoietic-stem-cells-to-multipotent-progenitors
#2
Xiang Yu, Chao Wu, Dheeraj Bhavanasi, Hong Wang, Brian D Gregory, Jian Huang
ATAC-seq provides genome-wide chromatin state in 3 cell types of hematopoietic stem/progenitor cells.Transcription factor cohorts are associated with dynamic changes of open chromatin during the differentiation of LT/ST-HSCs to MPPs.
June 13, 2017: Blood Advances
https://www.readbyqxmd.com/read/29259032/analysis-of-chromatin-accessibility-in-decidualizing-human-endometrial-stromal-cells
#3
Pavle Vrljicak, Emma S Lucas, Lauren Lansdowne, Raffaella Lucciola, Joanne Muter, Nigel P Dyer, Jan J Brosens, Sascha Ott
Spontaneous decidualization of the endometrium in response to progesterone signaling is confined to menstruating species, including humans and other higher primates. During this process, endometrial stromal cells (EnSCs) differentiate into specialized decidual cells that control embryo implantation. We subjected undifferentiated and decidualizing human EnSCs to an assay for transposase accessible chromatin with sequencing (ATAC-seq) to map the underlying chromatin changes. A total of 185,084 open DNA loci were mapped accurately in EnSCs...
December 19, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29249357/il-10-signaling-remodels-adipose-chromatin-architecture-to-limit-thermogenesis-and-energy-expenditure
#4
Prashant Rajbhandari, Brandon J Thomas, An-Chieh Feng, Cynthia Hong, Jiexin Wang, Laurent Vergnes, Tamer Sallam, Bo Wang, Jaspreet Sandhu, Marcus M Seldin, Aldons J Lusis, Loren G Fong, Melanie Katz, Richard Lee, Stephen G Young, Karen Reue, Stephen T Smale, Peter Tontonoz
Signaling pathways that promote adipose tissue thermogenesis are well characterized, but the limiters of energy expenditure are largely unknown. Here, we show that ablation of the anti-inflammatory cytokine IL-10 improves insulin sensitivity, protects against diet-induced obesity, and elicits the browning of white adipose tissue. Mechanistic studies define bone marrow cells as the source of the IL-10 signal and adipocytes as the target cell type mediating these effects. IL-10 receptor alpha is highly enriched in mature adipocytes and is induced in response to differentiation, obesity, and aging...
December 8, 2017: Cell
https://www.readbyqxmd.com/read/29229750/profiling-of-accessible-chromatin-regions-across-multiple-plant-species-and-cell-types-reveals-common-gene-regulatory-principles-and-new-control-modules
#5
Kelsey A Maher, Marko Bajic, Kaisa Kajala, Mauricio Reynoso, Germain Pauluzzi, Donnelly West, Kristina Zumstein, Margaret Woodhouse, Kerry L Bubb, Michael W Dorrity, Christine Queitsch, Julia Bailey-Serres, Neelima Sinha, Siobhan M Brady, Roger Deal
The transcriptional regulatory structure of plant genomes remains poorly defined relative to animals. It is unclear how many cis-regulatory elements exist, where these elements lie relative to promoters, and how these features are conserved across plant species. We employed the Assay for Transposase-Accessible Chromatin (ATAC-seq) in four plant species (Arabidopsis thaliana, Medicago truncatula, Solanum lycopersicum, and Oryza sativa) to delineate open chromatin regions and transcription factor (TF) binding sites across each genome...
December 11, 2017: Plant Cell
https://www.readbyqxmd.com/read/29220666/chromatin-accessibility-dynamics-during-ipsc-reprogramming
#6
Dongwei Li, Jing Liu, Xuejie Yang, Chunhua Zhou, Jing Guo, Chuman Wu, Yue Qin, Lin Guo, Jiangping He, Shenyong Yu, He Liu, Xiaoshan Wang, Fang Wu, Junqi Kuang, Andrew P Hutchins, Jiekai Chen, Duanqing Pei
Cell-fate decisions remain poorly understood at the chromatin level. Here, we map chromatin remodeling dynamics during induction of pluripotent stem cells. ATAC-seq profiling of MEFs expressing Oct4-Sox2-Klf4 (OSK) reveals dynamic changes in chromatin states shifting from open to closed (OC) and closed to open (CO), with an initial burst of OC and an ending surge of CO. The OC loci are largely composed of genes associated with a somatic fate, while the CO loci are associated with pluripotency. Factors/conditions known to impede reprogramming prevent OSK-driven OC and skew OC-CO dynamics...
December 7, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29181276/i-atac-interactive-pipeline-for-the-management-and-pre-processing-of-atac-seq-samples
#7
Zeeshan Ahmed, Duygu Ucar
Assay for Transposase Accessible Chromatin (ATAC-seq) is an open chromatin profiling assay that is adapted to interrogate chromatin accessibility from small cell numbers. ATAC-seq surmounted a major technical barrier and enabled epigenome profiling of clinical samples. With this advancement in technology, we are now accumulating ATAC-seq samples from clinical samples at an unprecedented rate. These epigenomic profiles hold the key to uncovering how transcriptional programs are established in diverse human cells and are disrupted by genetic or environmental factors...
2017: PeerJ
https://www.readbyqxmd.com/read/29155775/mapping-genome-wide-accessible-chromatin-in-primary-human-t-lymphocytes-by-atac-seq
#8
Ivana Grbesa, Miriam Tannenbaum, Avital Sarusi-Portuguez, Michal Schwartz, Ofir Hakim
Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) is a method used for the identification of open (accessible) regions of chromatin. These regions represent regulatory DNA elements (e.g., promoters, enhancers, locus control regions, insulators) to which transcription factors bind. Mapping the accessible chromatin landscape is a powerful approach for uncovering active regulatory elements across the genome. This information serves as an unbiased approach for discovering the network of relevant transcription factors and mechanisms of chromatin structure that govern gene expression programs...
November 13, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29141961/chromatin-accessibility-dynamics-reveal-novel-functional-enhancers-in-c-elegans
#9
Aaron C Daugherty, Robin W Yeo, Jason D Buenrostro, William J Greenleaf, Anshul Kundaje, Anne Brunet
Chromatin accessibility, a crucial component of genome regulation, has primarily been studied in homogeneous and simple systems, such as isolated cell populations or early-development models. Whether chromatin accessibility can be assessed in complex, dynamic systems in vivo with high sensitivity remains largely unexplored. In this study, we use ATAC-seq to identify chromatin accessibility changes in a whole animal, the model organism Caenorhabditis elegans, from embryogenesis to adulthood. Chromatin accessibility changes between developmental stages are highly reproducible, recapitulate histone modification changes, and reveal key regulatory aspects of the epigenomic landscape throughout organismal development...
December 2017: Genome Research
https://www.readbyqxmd.com/read/29133016/dynamic-transcriptional-control-of-macrophage-mirna-signature-via-inflammation-responsive-enhancers-revealed-using-a-combination-of-next-generation-sequencing-based-approaches
#10
Zsolt Czimmerer, Attila Horvath, Bence Daniel, Gergely Nagy, Ixchelt Cuaranta-Monroy, Mate Kiss, Zsuzsanna Kolostyak, Szilard Poliska, Laszlo Steiner, Nikolas Giannakis, Tamas Varga, Laszlo Nagy
MicroRNAs are important components of the post-transcriptional fine-tuning of macrophage gene expression in physiological and pathological conditions. However, the mechanistic underpinnings and the cis-acting genomic factors of how macrophage polarizing signals induce miRNA expression changes are not well characterized. Therefore, we systematically evaluated the transcriptional basis underlying the inflammation-mediated regulation of macrophage microRNome using the combination of different next generation sequencing datasets...
November 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29126307/universal-correction-of-enzymatic-sequence-bias-reveals-molecular-signatures-of-protein-dna-interactions
#11
André L Martins, Ninad M Walavalkar, Warren D Anderson, Chongzhi Zang, Michael J Guertin
Coupling molecular biology to high-throughput sequencing has revolutionized the study of biology. Molecular genomics techniques are continually refined to provide higher resolution mapping of nucleic acid interactions and structure. Sequence preferences of enzymes can interfere with the accurate interpretation of these data. We developed seqOutBias to characterize enzymatic sequence bias from experimental data and scale individual sequence reads to correct intrinsic enzymatic sequence biases. SeqOutBias efficiently corrects DNase-seq, TACh-seq, ATAC-seq, MNase-seq and PRO-seq data...
November 8, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29126117/dynamic-reorganization-of-open-chromatin-underlies-diverse-transcriptomes-during-spermatogenesis
#12
So Maezawa, Masashi Yukawa, Kris G Alavattam, Artem Barski, Satoshi H Namekawa
During spermatogenesis, germ cells undergo massive cellular reconstruction and dynamic chromatin remodeling to facilitate highly diverse transcriptomes, which are required for the production of functional sperm. However, it remains unknown how germline chromatin is organized to promote the dynamic, complex transcriptomes of spermatogenesis. Here, using ATAC-seq, we establish the varied landscape of open chromatin during spermatogenesis. We identify the reorganization of accessible chromatin in intergenic and intronic regions during the mitosis-to-meiosis transition...
November 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29107597/naked-mole-rat-cells-have-a-stable-epigenome-that-resists-ipsc%C3%A2-reprogramming
#13
Li Tan, Zhonghe Ke, Gregory Tombline, Nicholas Macoretta, Kevin Hayes, Xiao Tian, Ruitu Lv, Julia Ablaeva, Michael Gilbert, Natarajan V Bhanu, Zuo-Fei Yuan, Benjamin A Garcia, Yujiang G Shi, Yang Shi, Andrei Seluanov, Vera Gorbunova
Naked mole rat (NMR) is a valuable model for aging and cancer research due to its exceptional longevity and cancer resistance. We observed that the reprogramming efficiency of NMR fibroblasts in response to OSKM was drastically lower than that of mouse fibroblasts. Expression of SV40 LargeT antigen (LT) dramatically improved reprogramming of NMR fibroblasts. Inactivation of Rb alone, but not p53, was sufficient to improve reprogramming efficiency, suggesting that NMR chromatin may be refractory to reprogramming...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29107594/genes-associated-with-pancreas-development-and-function-maintain-open-chromatin-in-ipscs-generated-from-human-pancreatic-beta-cells
#14
Matthias Thurner, Liraz Shenhav, Agata Wesolowska-Andersen, Amanda J Bennett, Amy Barrett, Anna L Gloyn, Mark I McCarthy, Nicola L Beer, Shimon Efrat
Current in vitro islet differentiation protocols suffer from heterogeneity and low efficiency. Induced pluripotent stem cells (iPSCs) derived from pancreatic beta cells (BiPSCs) preferentially differentiate toward endocrine pancreas-like cells versus those from fibroblasts (FiPSCs). We interrogated genome-wide open chromatin in BiPSCs and FiPSCs via ATAC-seq and identified ∼8.3k significant, differential open chromatin sites (DOCS) between the two iPSC subtypes (false discovery rate [FDR] < 0.05). DOCS where chromatin was more accessible in BiPSCs (Bi-DOCS) were significantly enriched for known regulators of endodermal development, including bivalent and weak enhancers, and FOXA2 binding sites (FDR < 0...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29104531/the-repression-of-atoh1-by-neurogenin1-during-inner-ear-development
#15
Héctor Gálvez, Juan J Tena, Fernando Giraldez, Gina Abelló
Atonal homolog 1 (Atoh1) and Neurogenin1 (Neurog1) are basic Helix-Loop-Helix (bHLH) transcription factors crucial for the generation of hair cells (HCs) and neurons in the inner ear. Both genes are induced early in development, but the expression of Atoh1 is counteracted by Neurog1. As a result, HC development is prevented during neurogenesis. This work aimed at understanding the molecular basis of this interaction. Atoh1 regulation depends on a 3'Atoh1-enhancer that is the site for Atoh1 autoregulation. Reporter assays on chick embryos and P19 cells show that Neurog1 hampers the autoactivation of Atoh1, the effect being cell autonomous and independent on Notch activity...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29067999/myd88-dependent-dendritic-and-epithelial-cell-crosstalk-orchestrates-immune-responses-to-allergens
#16
S Y Thomas, G S Whitehead, M Takaku, J M Ward, X Xu, K Nakano, M R Lyons-Cohen, H Nakano, K M Gowdy, P A Wade, D N Cook
Sensitization to inhaled allergens is dependent on activation of conventional dendritic cells (cDCs) and on the adaptor molecule, MyD88. However, many cell types in the lung express Myd88, and it is unclear how signaling in these different cell types reprograms cDCs and leads to allergic inflammation of the airway. By combining ATAC-seq with RNA profiling, we found that MyD88 signaling in cDCs maintained open chromatin at select loci even at steady state, allowing genes to be rapidly induced during allergic sensitization...
October 25, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29066026/cd4-cd28-kir-cd11a-hi-t-cells-correlate-with-disease-activity-and-are-characterized-by-a-pro-inflammatory-epigenetic-and-transcriptional-profile-in-lupus-patients
#17
Elizabeth Gensterblum, Paul Renauer, Patrick Coit, Faith M Strickland, Nathan C Kilian, Shaylynn Miller, Mikhail Ognenovski, Jonathan D Wren, Pei-Suen Tsou, Emily E Lewis, Kathleen Maksimowicz-McKinnon, W Joseph McCune, Bruce C Richardson, Amr H Sawalha
OBJECTIVE: The goal of this study was to comprehensively characterize CD4+CD28+ T cells overexpressing CD11a and KIR genes, and examine the relationship between this T cell subset, genetic risk, and disease activity in lupus. METHODS: The size of the CD4+CD28+KIR+CD11a(hi) T cell subset was determined by flow cytometry, and total genetic risk for lupus was calculated in 105 female patients using 43 confirmed genetic susceptibility loci. Primary CD4+CD28+KIR+CD11a(hi) T cells were isolated from lupus patients or were induced from healthy individuals using 5-azacytidine...
October 20, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29052193/identification-of-open-chromatin-regions-in-plant-genomes-using-atac-seq
#18
Marko Bajic, Kelsey A Maher, Roger B Deal
Identifying and characterizing highly accessible chromatin regions assists in determining the location of genomic regulatory elements and understanding transcriptional regulation. In this chapter, we describe an approach to map accessible chromatin features in plants using the Assay for Transposase-Accessible Chromatin, combined with high-throughput sequencing (ATAC-seq), which was originally developed for cultured animal cells. This technique utilizes a hyperactive Tn5 transposase to cause DNA cleavage and simultaneous insertion of sequencing adapters into open chromatin regions of the input nuclei...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29046480/epigenetic-mechanisms-underlying-maternal-diabetes-associated-risk-of-congenital-heart-disease
#19
Madhumita Basu, Jun-Yi Zhu, Stephanie LaHaye, Uddalak Majumdar, Kai Jiao, Zhe Han, Vidu Garg
Birth defects are the leading cause of infant mortality, and they are caused by a combination of genetic and environmental factors. Environmental risk factors may contribute to birth defects in genetically susceptible infants by altering critical molecular pathways during embryogenesis, but experimental evidence for gene-environment interactions is limited. Fetal hyperglycemia associated with maternal diabetes results in a 5-fold increased risk of congenital heart disease (CHD), but the molecular basis for this correlation is unknown...
October 19, 2017: JCI Insight
https://www.readbyqxmd.com/read/29038474/a-shared-runx1-bound-zbtb16-enhancer-directs-innate-and-innate-like-lymphoid-lineage-development
#20
Ai-Ping Mao, Isabel E Ishizuka, Darshan N Kasal, Malay Mandal, Albert Bendelac
Zbtb16-encoded PLZF is a signature transcription factor (TF) that directs the acquisition of T-helper effector programs during the development of multiple innate lymphocyte lineages, including natural killer T cell, innate lymphoid cell, mucosal-associated invariant T cell and γδ lineages. PLZF is also essential in osteoblast and spermatogonial development. How Zbtb16 itself is regulated in different lineages is incompletely understood. Here, by systematic CRISPR/Cas9-assisted deletions of chromatin accessible regions within the Zbtb16 locus in mouse, we identify a critical enhancer controlling PLZF expression exclusively in innate lymphoid lineages...
October 16, 2017: Nature Communications
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