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ATAC-seq

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https://www.readbyqxmd.com/read/29141961/chromatin-accessibility-dynamics-reveal-novel-functional-enhancers-in-c-elegans
#1
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...
November 15, 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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/29030848/profiling-open-chromatin-structure-in-the%C3%A2-ovarian-somatic-cells-using-atac-seq
#13
Kensaku Murano, Yuka W Iwasaki, Haruhiko Siomi
The assay for transposase-accessible chromatin using sequencing (ATAC-seq) was recently established as a method to profile open chromatin, which overcomes the sample size limitations of the alternative methods DNase/MNase-seq. To investigate the role of Piwi in heterochromatin formation around transposable element loci, we have used ATAC-seq to examine chromatin accessibility at target transposable elements in a Drosophila cultured cell line, ovarian somatic cells (OSCs). In this chapter, we describe our method to profile open chromatin structure in OSCs using ATAC-seq...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29023442/environmental-perturbations-lead-to-extensive-directional-shifts-in-rna-processing
#14
Allison L Richards, Donovan Watza, Anthony Findley, Adnan Alazizi, Xiaoquan Wen, Athma A Pai, Roger Pique-Regi, Francesca Luca
Environmental perturbations have large effects on both organismal and cellular traits, including gene expression, but the extent to which the environment affects RNA processing remains largely uncharacterized. Recent studies have identified a large number of genetic variants associated with variation in RNA processing that also have an important role in complex traits; yet we do not know in which contexts the different underlying isoforms are used. Here, we comprehensively characterized changes in RNA processing events across 89 environments in five human cell types and identified 15,300 event shifts (FDR = 15%) comprised of eight event types in over 4,000 genes...
October 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29020802/recent-advances-in-the-systems-biology-of-aging
#15
Daniel Edward Lee Promislow, Mark A McCormick
<b><i>Significance</i></b>: Reductionist studies have contributed greatly to our understanding of the basic biology of aging in recent years but we still do not understand fundamental mechanisms for many identified drugs and pathways. Use of systems approaches will help us move forward in our understanding of aging. <b><i>Recent Advances</i></b>: Recent work described here has illustrated the power of systems biology to inform our understanding of aging through the study of 1) diet restriction; 2) neurodegenerative disease; and 3) biomarkers of aging...
October 12, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28986391/altered-hydroxymethylation-is-seen-at-regulatory-regions-in-pancreatic-cancer-and-regulates-oncogenic-pathways
#16
Sanchari Bhattacharyya, Kith Pradhan, Nathaniel Campbell, Jozef Mazdo, Aparna Vasantkumar, Shahina Maqbool, Tushar D Bhagat, Sonal Gupta, Masako Suzuki, Yiting Yu, John M Greally, Ulrich Steidl, James Bradner, Meelad Dawlaty, Lucy Godley, Anirban Maitra, Amit Verma
Transcriptional deregulation of oncogenic pathways is a hallmark of cancer and can be due to epigenetic alterations. 5-Hydroxymethylcytosine (5-hmC) is an epigenetic modification that has not been studied in pancreatic cancer. Genome-wide analysis of 5-hmC-enriched loci with hmC-seal was conducted in a cohort of low-passage pancreatic cancer cell lines, primary patient-derived xenografts, and pancreatic controls and revealed strikingly altered patterns in neoplastic tissues. Differentially hydroxymethylated regions preferentially affected known regulatory regions of the genome, specifically overlapping with known H3K4me1 enhancers...
November 2017: Genome Research
https://www.readbyqxmd.com/read/28985528/chromatin-and-single-cell-rna-seq-profiling-reveal-dynamic-signaling-and-metabolic-transitions-during-human-spermatogonial-stem-cell-development
#17
Jingtao Guo, Edward J Grow, Chongil Yi, Hana Mlcochova, Geoffrey J Maher, Cecilia Lindskog, Patrick J Murphy, Candice L Wike, Douglas T Carrell, Anne Goriely, James M Hotaling, Bradley R Cairns
Human adult spermatogonial stem cells (hSSCs) must balance self-renewal and differentiation. To understand how this is achieved, we profiled DNA methylation and open chromatin (ATAC-seq) in SSEA4(+) hSSCs, analyzed bulk and single-cell RNA transcriptomes (RNA-seq) in SSEA4(+) hSSCs and differentiating c-KIT(+) spermatogonia, and performed validation studies via immunofluorescence. First, DNA hypomethylation at embryonic developmental genes supports their epigenetic "poising" in hSSCs for future/embryonic expression, while core pluripotency genes (OCT4 and NANOG) were transcriptionally and epigenetically repressed...
October 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28973438/p53-regulates-enhancer-accessibility-and-activity-in-response-to-dna-damage
#18
Scott T Younger, John L Rinn
The tumor suppressor p53 is a well-characterized transcription factor that can bind gene promoters and regulate target gene transcription in response to DNA damage. Recent studies, however, have revealed that p53 binding events occur predominantly within regulatory enhancer elements. The effect of p53 binding on enhancer function has not been systematically evaluated. Here, we perform a genome-scale analysis of enhancer activity from p53-bound sequences using a series of massively parallel reporter assays (MPRAs) coupled with the assay for transposase-accessible chromatin (ATAC-Seq)...
September 29, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28967863/chromatin-accessibility-underlies-synthetic-lethality-of-swi-snf-subunits-in-arid1a-mutant-cancers
#19
Timothy W R Kelso, Devin K Porter, Maria Luisa Amaral, Maxim N Shokhirev, Christopher Benner, Diana C Hargreaves
ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, is frequently mutated in cancer. Deficiency in its homolog ARID1B is synthetically lethal with ARID1A mutation. However, the functional relationship between these homologs has not been explored. Here, we use ATAC-seq, genome-wide histone modification mapping, and expression analysis to examine colorectal cancer cells lacking one or both ARID proteins. We find that ARID1A has a dominant role in maintaining chromatin accessibility at enhancers, while the contribution of ARID1B is evident only in the context of ARID1A mutation...
October 2, 2017: ELife
https://www.readbyqxmd.com/read/28931935/alpha-tc1-and-beta-tc-6-genomic-profiling-uncovers-both-shared-and-distinct-transcriptional-regulatory-features-with-their-primary-islet-counterparts
#20
Nathan Lawlor, Ahrim Youn, Romy Kursawe, Duygu Ucar, Michael L Stitzel
Alpha TC1 (αTC1) and Beta-TC-6 (βTC6) mouse islet cell lines are cellular models of islet (dys)function and type 2 diabetes (T2D). However, genomic characteristics of these cells, and their similarities to primary islet alpha and beta cells, are undefined. Here, we report the epigenomic (ATAC-seq) and transcriptomic (RNA-seq) landscapes of αTC1 and βTC6 cells. Each cell type exhibits hallmarks of its primary islet cell counterpart including cell-specific expression of beta (e.g., Pdx1) and alpha (e.g., Arx) cell transcription factors (TFs), and enrichment of binding motifs for these TFs in αTC1/βTC6 cis-regulatory elements...
September 20, 2017: Scientific Reports
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