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https://www.readbyqxmd.com/read/28381412/the-ddr-at-telomeres-lacking-intact-shelterin-does-not-require-substantial-chromatin-decompaction
#1
Leonid A Timashev, Hazen Babcock, Xiaowei Zhuang, Titia de Lange
Telomeres are protected by shelterin, a six-subunit protein complex that represses the DNA damage response (DDR) at chromosome ends. Extensive data suggest that TRF2 in shelterin remodels telomeres into the t-loop structure, thereby hiding telomere ends from double-stranded break repair and ATM signaling, whereas POT1 represses ATR signaling by excluding RPA. An alternative protection mechanism was suggested recently by which shelterin subunits TRF1, TRF2, and TIN2 mediate telomeric chromatin compaction, which was proposed to minimize access of DDR factors...
March 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28369967/a-simulation-study-to-compare-the-treatment-effect-of-tamoxifen-by-cyp2d6-genotypes-and-third-generation-aromatase-inhibitors
#2
Gwan Cheol Park, Jin-A Jung, Kyun-Seop Bae, Hyeong-Seok Lim
Some prospective, randomized clinical trials, including ATAC and BIG 1-98, demonstrated superior treatment effect of third-generation aromatase inhibitors (AIs) versus tamoxifen in postoperative therapy for patients with breast cancer. In retrospective genotyping analyses of the 2 studies using tumor samples, no difference in the treatment effect of tamoxifen was observed by CYP2D6 genotypes. However, those analyses did not consider loss of heterozygosity that could have occurred when genotyping using tumor tissue...
April 3, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28365152/dynamic-gene-regulatory-networks-of-human-myeloid-differentiation
#3
Ricardo N Ramirez, Nicole C El-Ali, Mikayla Anne Mager, Dana Wyman, Ana Conesa, Ali Mortazavi
The reconstruction of gene regulatory networks underlying cell differentiation from high-throughput gene expression and chromatin data remains a challenge. Here, we derive dynamic gene regulatory networks for human myeloid differentiation using a 5-day time series of RNA-seq and ATAC-seq data. We profile HL-60 promyelocytes differentiating into macrophages, neutrophils, monocytes, and monocyte-derived macrophages. We find a rapid response in the expression of key transcription factors and lineage markers that only regulate a subset of their targets at a given time, which is followed by chromatin accessibility changes that occur later along with further gene expression changes...
March 27, 2017: Cell Systems
https://www.readbyqxmd.com/read/28360229/aortic-calcification-onset-and-progression-association-with-the-development-of-coronary-atherosclerosis
#4
Hagen Kälsch, Nils Lehmann, Susanne Moebus, Barbara Hoffmann, Andreas Stang, Karl-Heinz Jöckel, Raimund Erbel, Amir A Mahabadi
BACKGROUND: Thoracic aortic calcification (TAC) and coronary artery calcification (CAC) are markers of subclinical atherosclerosis and are associated with incident major cardiovascular events. We investigated major determinants for incidence and progression of TAC and the association between TAC and CAC incidence and progression. METHODS AND RESULTS: In a population-based cohort study, 3270 participants (aged 45-74 years, 53.1% women) received cardiac computed tomography at baseline and after a mean follow-up of 5...
March 30, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28356342/widespread-changes-in-nucleosome-accessibility-without-changes-in-nucleosome-occupancy-during-a-rapid-transcriptional-induction
#5
Britta Mueller, Jakub Mieczkowski, Sharmistha Kundu, Peggy Wang, Ruslan Sadreyev, Michael Y Tolstorukov, Robert E Kingston
Activation of transcription requires alteration of chromatin by complexes that increase the accessibility of nucleosomal DNA. Removing nucleosomes from regulatory sequences has been proposed to play a significant role in activation. We tested whether changes in nucleosome occupancy occurred on the set of genes that is activated by the unfolded protein response (UPR). We observed no decrease in occupancy on most promoters, gene bodies, and enhancers. Instead, there was an increase in the accessibility of nucleosomes, as measured by micrococcal nuclease (MNase) digestion and ATAC-seq (assay for transposase-accessible chromatin [ATAC] using sequencing), that did not result from removal of the nucleosome...
March 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28350380/transcriptomic-profiling-of-39-commonly-used-neuroblastoma-cell-lines
#6
Jo Lynne Harenza, Maura A Diamond, Rebecca N Adams, Michael M Song, Heather L Davidson, Lori S Hart, Maiah H Dent, Paolo Fortina, C Patrick Reynolds, John M Maris
Neuroblastoma cell lines are an important and cost-effective model used to study oncogenic drivers of the disease. While many of these cell lines have been previously characterized with SNP, methylation, and/or mRNA expression microarrays, there has not been an effort to comprehensively sequence these cell lines. Here, we present raw whole transcriptome data generated by RNA sequencing of 39 commonly-used neuroblastoma cell lines. These data can be used to perform differential expression analysis based on a genetic aberration or phenotype in neuroblastoma (e...
March 28, 2017: Scientific Data
https://www.readbyqxmd.com/read/28335009/open-chromatin-profiling-of-human-postmortem-brain-infers-functional-roles-for-non-coding-schizophrenia-loci
#7
John F Fullard, Claudia Giambartolomei, Mads E Hauberg, Ke Xu, Georgios Voloudakis, Zhiping Shao, Christopher Bare, Joel T Dudley, Manuel Mattheisen, Nikolaos K Robakis, Vahram Haroutunian, Panos Roussos
Open chromatin provides access to DNA binding proteins for the correct spatiotemporal regulation of gene expression. Mapping chromatin accessibility has been widely used to identify the location of cis regulatory elements (CREs) including promoters and enhancers. CREs show tissue- and cell-type specificity and disease-associated variants are often enriched for CREs in the tissues and cells that pertain to a given disease. To better understand the role of CREs in neuropsychiatric disorders we applied the Assay for Transposase Accessible Chromatin followed by sequencing (ATAC-seq) to neuronal and non-neuronal nuclei isolated from frozen postmortem human brain by fluorescence-activated nuclear sorting (FANS)...
March 14, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28279124/effect-of-maternal-and-neonatal-interleukin-6-174%C3%A2-g-c-polymorphism-on-preterm-birth-and-neonatal-morbidity
#8
N M Karakaş, A Ecevit, Y Yalçın, B Özdemir, H Verdi, M A Tekindal, N Y Özbek, A Tarcan, F B Ataç, A Haberal
OBJECTIVE: The aim of this study was to analyze maternal and neonatal interleukin 6 (IL-6) (-174 G/C) polymorphism and to determine effect on preterm birth and neonatal morbidity. STUDY DESIGN: 164 mothers (100 term births, 64 preterm births) and 183 newborn infants who were 100 healthy term and 83 preterm babies followed in newborn intensive care units were evaluated. PCR-RFLP was performed for IL-6 (-174 G/C) genotyping. RESULTS: The rate of GG genotype in mothers of term and preterm infants were 54% (n = 54/100), 75% (n = 48/64), respectively (p> 0...
March 9, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28256534/cell-type-specific-epigenomic-analysis-reveals-a-uniquely-closed-chromatin-architecture-in-mouse-rod-photoreceptors
#9
Andrew E O Hughes, Jennifer M Enright, Connie A Myers, Susan Q Shen, Joseph C Corbo
Rod photoreceptors are specialized neurons that mediate vision in dim light and are the predominant photoreceptor type in nocturnal mammals. The rods of nocturnal mammals are unique among vertebrate cell types in having an 'inverted' nuclear architecture, with a dense mass of heterochromatin in the center of the nucleus rather than dispersed clumps at the periphery. To test if this unique nuclear architecture is correlated with a unique epigenomic landscape, we performed ATAC-seq on mouse rods and their most closely related cell type, cone photoreceptors...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28252242/extended-adjuvant-endocrine-therapy-in-breast-cancer-evidence-and-update-a-review
#10
Marcel Jinih, Norma Relihan, Mark A Corrigan, Seamus O'Reilly, Henry P Redmond
The optimal duration and treatment strategies involving adjuvant endocrine therapy in early breast cancer remained largely undetermined. As data emerge on the various modalities of treatment in both pre- and postmenopausal groups, debates, and discussions continue. Most studies to date focused on the 5-year duration of treatment consisting of mainly tamoxifen. The Arimidex, Tamoxifen, Alone or in Combination (ATAC) study demonstrated that anastrozole is superior to tamoxifen and has become the mainstream treatment in postmenopausal women with early breast cancer, although the duration was arbitrarily set for 5 years, analogous to tamoxifen treatment...
March 2, 2017: Breast Journal
https://www.readbyqxmd.com/read/28247118/do-bilateral-and-unilateral-greater-occipital-nerve-block-effectiveness-differ-in-chronic-migraine-patients
#11
Hanzade Aybüke Ünal-Artık, Levent Ertuğrul İnan, Ceyla Ataç-Uçar, Tahir Kurtuluş Yoldaş
We aimed to compare the effectiveness of bilateral and unilateral block application in chronic migraine patients and whether there were differences in their effectiveness retrospectively. In chronic migraine patients undergoing Greater occipital nerve (GON) block, mean number of days with pain per month before and after block, mean duration of pain in attacks (in hours), and mean Visual Analog Scale (VAS) in attack and pain severity were recorded from files. The patients underwent one block a week for the first 1 month, thereafter one block a month according to GON block protocol used by our institute...
February 28, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28239551/genome-wide-chromatin-accessibility-dna-methylation-and-gene-expression-analysis-of-histone-deacetylase-inhibition-in-triple-negative-breast-cancer
#12
Matias A Bustos, Matthew P Salomon, Nellie Nelson, Sandy C Hsu, Maggie L DiNome, Dave S B Hoon, Diego M Marzese
Triple-negative breast cancer (TNBC), especially the subset with a basal phenotype, represents the most aggressive subtype of breast cancer. Unlike other solid tumors, TNBCs harbor a low number of driver mutations. Conversely, we and others have demonstrated a significant impact of epigenetic alterations, including DNA methylation and histone post-translational modifications, affecting TNBCs. Due to the promising results in pre-clinical studies, histone deacetylase inhibitors (HDACi) are currently being tested in several clinical trials for breast cancer and other solid tumors...
June 2017: Genomics Data
https://www.readbyqxmd.com/read/28230047/electrically-tunable-artificial-gauge-potential-for-polaritons
#13
Hyang-Tag Lim, Emre Togan, Martin Kroner, Javier Miguel-Sanchez, Atac Imamoğlu
Neutral particles subject to artificial gauge potentials can behave as charged particles in magnetic fields. This fascinating premise has led to demonstrations of one-way waveguides, topologically protected edge states and Landau levels for photons. In ultracold neutral atoms, effective gauge fields have allowed the emulation of matter under strong magnetic fields leading to realization of Harper-Hofstadter and Haldane models. Here we show that application of perpendicular electric and magnetic fields effects a tunable artificial gauge potential for two-dimensional microcavity exciton polaritons...
February 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28211918/myotonic-dystrophy-type-1-patient-derived-ipscs-for-the-investigation-of-ctg-repeat-instability
#14
Junko Ueki, Masayuki Nakamori, Masahiro Nakamura, Misato Nishikawa, Yoshinori Yoshida, Azusa Tanaka, Asuka Morizane, Masayoshi Kamon, Toshiyuki Araki, Masanori P Takahashi, Akira Watanabe, Nobuya Inagaki, Hidetoshi Sakurai
Myotonic dystrophy type 1 (DM1) is an autosomal-dominant multi-system disease caused by expanded CTG repeats in dystrophia myotonica protein kinase (DMPK). The expanded CTG repeats are unstable and can increase the length of the gene with age, which worsens the symptoms. In order to establish a human stem cell system suitable for the investigation of repeat instability, DM1 patient-derived iPSCs were generated and differentiated into three cell types commonly affected in DM1, namely cardiomyocytes, neurons and myocytes...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28193859/genetic-regulatory-signatures-underlying-islet-gene-expression-and-type-2-diabetes
#15
Arushi Varshney, Laura J Scott, Ryan P Welch, Michael R Erdos, Peter S Chines, Narisu Narisu, Ricardo D'O Albanus, Peter Orchard, Brooke N Wolford, Romy Kursawe, Swarooparani Vadlamudi, Maren E Cannon, John P Didion, John Hensley, Anthony Kirilusha, Lori L Bonnycastle, D Leland Taylor, Richard Watanabe, Karen L Mohlke, Michael Boehnke, Francis S Collins, Stephen C J Parker, Michael L Stitzel
Genome-wide association studies (GWAS) have identified >100 independent SNPs that modulate the risk of type 2 diabetes (T2D) and related traits. However, the pathogenic mechanisms of most of these SNPs remain elusive. Here, we examined genomic, epigenomic, and transcriptomic profiles in human pancreatic islets to understand the links between genetic variation, chromatin landscape, and gene expression in the context of T2D. We first integrated genome and transcriptome variation across 112 islet samples to produce dense cis-expression quantitative trait loci (cis-eQTL) maps...
February 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28174238/functional-characterisation-of-cis-regulatory-elements-governing-dynamic-eomes-expression-in-the-early-mouse-embryo
#16
Claire S Simon, Damien J Downes, Matthew E Gosden, Jelena Telenius, Douglas R Higgs, Jim R Hughes, Ita Costello, Elizabeth K Bikoff, Elizabeth J Robertson
The T-box transcription factor (TF) Eomes is a key regulator of cell fate decisions during early mouse development. The cis-acting regulatory elements that direct expression in the anterior visceral endoderm (AVE), primitive streak (PS) and definitive endoderm (DE) have yet to be defined. Here, we identified three gene-proximal enhancer-like sequences (PSE_a, PSE_b and VPE) that faithfully activate tissue specific expression in transgenic embryos. However, targeted deletion experiments demonstrate that PSE_a and PSE_b are dispensable and only the VPE is required for optimal Eomes expression in vivo Embryos lacking this enhancer display variably penetrant defects in anterior-posterior axis orientation and DE formation...
February 7, 2017: Development
https://www.readbyqxmd.com/read/28166220/neuronal-activity-modifies-the-chromatin-accessibility-landscape-in-the-adult-brain
#17
Yijing Su, Jaehoon Shin, Chun Zhong, Sabrina Wang, Prith Roychowdhury, Jongseuk Lim, David Kim, Guo-Li Ming, Hongjun Song
Neuronal activity-induced gene expression modulates the function and plasticity of the nervous system. It is unknown whether and to what extent neuronal activity may trigger changes in chromatin accessibility, a major mode of epigenetic regulation of gene expression. Here we compared chromatin accessibility landscapes of adult mouse dentate granule neurons in vivo before and after synchronous neuronal activation using an assay for transposase-accessible chromatin using sequencing (ATAC-seq). We found genome-wide changes 1 h after activation, with enrichment of gained-open sites at active enhancer regions and at binding sites for AP1-complex components, including c-Fos...
March 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28157509/mnase-sensitive-complexes-in-yeast-nucleosomes-and-non-histone-barriers
#18
Răzvan V Chereji, Josefina Ocampo, David J Clark
Micrococcal nuclease (MNase) is commonly used to map nucleosomes genome-wide, but nucleosome maps are affected by the degree of digestion. It has been proposed that many yeast promoters are not nucleosome-free but instead occupied by easily digested, unstable, "fragile" nucleosomes. We analyzed the histone content of all MNase-sensitive complexes by MNase-ChIP-seq and sonication-ChIP-seq. We find that yeast promoters are predominantly bound by non-histone protein complexes, with little evidence for fragile nucleosomes...
February 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28138849/contiguity-preserving-transposition-sequencing-cpt-seq-for-genome-wide-haplotyping-assembly-and-single-cell-atac-seq
#19
Lena Christiansen, Sasan Amini, Fan Zhang, Mostafa Ronaghi, Kevin L Gunderson, Frank J Steemers
Most genomes to date have been sequenced without taking into account the diploid nature of the genome. However, the distribution of variants on each individual chromosome can (1) significantly impact gene regulation and protein function, (2) have important implications for analyses of population history and medical genetics, and (3) be of great value for accurate interpretation of medically relevant genetic variation. Here, we describe a comprehensive and detailed protocol for an ultra fast (<3 h library preparation), cost-effective, and scalable haplotyping method, named Contiguity Preserving Transposition sequencing or CPT-seq (Amini et al...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28120510/predicting-enhancer-activity-and-variant-impact-using-gkm-svm
#20
Michael A Beer
We participated in the Critical Assessment of Genome Interpretation eQTL challenge to further test computational models of regulatory variant impact and their association with human disease. Our prediction model is based on a discriminative gapped-kmer SVM (gkm-SVM) trained on genome-wide chromatin accessibility data in the cell type of interest. The comparisons with massively parallel reporter assays (MPRA) in lymphoblasts show that gkm-SVM is among the most accurate prediction models even though all other models used the MPRA data for model training, and gkm-SVM did not...
January 25, 2017: Human Mutation
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