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https://www.readbyqxmd.com/read/28211918/myotonic-dystrophy-type-1-patient-derived-ipscs-for-the-investigation-of-ctg-repeat-instability
#1
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
#2
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 13, 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
#3
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
#4
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...
February 6, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28157509/mnase-sensitive-complexes-in-yeast-nucleosomes-and-non-histone-barriers
#5
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
#6
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%C3%A2-enhancer-activity-and-variant-impact-using-gkm-svm
#7
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, while gkm-SVM did not...
January 25, 2017: Human Mutation
https://www.readbyqxmd.com/read/28112738/landscape-of-monoallelic-dna-accessibility-in-mouse-embryonic-stem-cells-and-neural-progenitor-cells
#8
Jin Xu, Ava C Carter, Anne-Valerie Gendrel, Mikael Attia, Joshua Loftus, William J Greenleaf, Robert Tibshirani, Edith Heard, Howard Y Chang
We developed an allele-specific assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) to genotype and profile active regulatory DNA across the genome. Using a mouse hybrid F1 system, we found that monoallelic DNA accessibility across autosomes was pervasive, developmentally programmed and composed of several patterns. Genetically determined accessibility was enriched at distal enhancers, but random monoallelically accessible (RAMA) elements were enriched at promoters and may act as gatekeepers of monoallelic mRNA expression...
January 23, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28112643/layer-specific-chromatin-accessibility-landscapes-reveal-regulatory-networks-in-adult-mouse-visual-cortex
#9
Lucas T Gray, Zizhen Yao, Thuc Nghi Nguyen, Tae Kyung Kim, Hongkui Zeng, Bosiljka Tasic
Mammalian cortex is a laminar structure, with each layer composed of a characteristic set of cell types with different morphological, electrophysiological, and connectional properties. Here, we define chromatin accessibility landscapes of major, layer-specific excitatory classes of neurons, and compare them to each other and to inhibitory cortical neurons using the Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq). We identify a large number of layer-specific accessible sites, and significant association with genes that are expressed in specific cortical layers...
January 23, 2017: ELife
https://www.readbyqxmd.com/read/28075484/assay-for-transposase-accessible-chromatin-using-sequencing-atac-seq-data-analysis
#10
Kristy L S Miskimen, E Ricky Chan, Jonathan L Haines
The study of epigenetic properties of the human genome, including structural modifications of DNA and chromatin, has increased tremendously as mounting evidence has demonstrated how much epigenetics affects human gene expression. Buenrostro et al. have developed a rapid method, requiring low numbers of living cells as input, for examining chromatin accessibility across the epigenome, known as the assay for transposase-accessible chromatin using sequencing (ATAC-seq). The overall goal of this unit is to provide a thorough ATAC-seq data analysis plan, as well as describe how primary human blood samples can be processed for use in ATAC-seq...
January 11, 2017: Current Protocols in Human Genetics
https://www.readbyqxmd.com/read/28045414/evaluation-of-left-atrial-mechanical-function-and-atrial-conduction-abnormalities-in-patients-with-isolated-bicuspid-aortic-valve
#11
Arif Arısoy, Kadriye Memiç, Selami Demirelli, Kayıhan Karaman, Fatih Altunkaş, Metin Karayakalı, Yusuf Karavelioğlu, Ataç Çelik
OBJECTIVE: Present study is an evaluation of left atrial (LA) mechanical and conduction function in patients with bicuspid aortic valve (BAV) without significant valve dysfunction, and an investigation of relationship between LA function and aortic elasticity. METHODS: Study population consisted of 34 isolated BAV patients (mean age: 34±13 years) and 29 healthy, age- and sex-matched volunteers (mean age: 30±10 years). LA volume was measured using biplane area-length method and LA active and passive emptying volume and fraction was calculated...
December 2016: Türk Kardiyoloji Derneği Arşivi: Türk Kardiyoloji Derneğinin Yayın Organıdır
https://www.readbyqxmd.com/read/28012628/syneresis-and-rheological-behaviors-of-set-yogurt-containing-green-tea-and-green-coffee-powders
#12
Özge Dönmez, Burçe Ataç Mogol, Vural Gökmen
This study aimed to investigate the effect of added green coffee powder (GCP) and green tea powder (GTP) on syneresis behavior and consistency of set yogurts. Adding GCP (1 or 2%) decreased syneresis rate. The effect of GTP on the syneresis rate was concentration dependent. In comparison to the control, GTP decreased syneresis rate when it was added at 0.02%, but it caused an increase when added at 2%. No significant difference was observed in the syneresis rates when GTP was added at 1 and 0.01%, until 14 and 7 d of storage, respectively...
February 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28011773/altre-workflow-for-defining-altered-regulatory-elements-using-chromatin-accessibility-data
#13
Elizabeth Baskin, Rick Farouni, Ewy A Mathé
: : Regulatory elements regulate gene transcription, and their location and accessibility is cell-type specific, particularly for enhancers. Mapping and comparing chromatin accessibility between different cell types may identify mechanisms involved in cellular development and disease progression. To streamline and simplify differential analysis of regulatory elements genome-wide using chromatin accessibility data, such as DNase-seq, ATAC-seq, we developed ALTRE (ALTered Regulatory Elements), an R package and associated R Shiny web app...
December 22, 2016: Bioinformatics
https://www.readbyqxmd.com/read/27996962/an-atlas-of-transcriptional-chromatin-accessibility-and-surface-marker-changes-in-human-mesoderm-development
#14
Pang Wei Koh, Rahul Sinha, Amira A Barkal, Rachel M Morganti, Angela Chen, Irving L Weissman, Lay Teng Ang, Anshul Kundaje, Kyle M Loh
Mesoderm is the developmental precursor to myriad human tissues including bone, heart, and skeletal muscle. Unravelling the molecular events through which these lineages become diversified from one another is integral to developmental biology and understanding changes in cellular fate. To this end, we developed an in vitro system to differentiate human pluripotent stem cells through primitive streak intermediates into paraxial mesoderm and its derivatives (somites, sclerotome, dermomyotome) and separately, into lateral mesoderm and its derivatives (cardiac mesoderm)...
December 20, 2016: Scientific Data
https://www.readbyqxmd.com/read/27993786/defcom-analysis-and-modeling-of-transcription-factor-binding-sites-using-a-motif-centric-genomic-footprinter
#15
Bryan Quach, Terrence S Furey
MOTIVATION: Identifying the locations of transcription factor binding sites is critical for understanding how gene transcription is regulated across different cell types and conditions. Chromatin accessibility experiments such as DNaseI sequencing (DNase-seq) and Assay for Transposase Accessible Chromatin sequencing (ATAC-seq) produce genome-wide data that include distinct "footprint" patterns at binding sites. Nearly all existing computational methods to detect footprints from these data assume that footprint signals are highly homogeneous across footprint sites...
December 19, 2016: Bioinformatics
https://www.readbyqxmd.com/read/27989964/histone-acetylation-of-glucose-induced-thioredoxin-interacting-protein-gene-expression-in-pancreatic-islets
#16
Pradeep Bompada, David Atac, Cheng Luan, Robin Andersson, Judit Domènech Omella, Emilia Ottosson Laakso, Jason Wright, Leif Groop, Yang De Marinis
Thioredoxin-interacting protein (TXNIP) has been shown to be associated with glucose-induced deterioration of pancreatic beta cell function in diabetes. However, whether epigenetic mechanisms contribute to the regulation of TXNIP gene expression by glucose is not clear. Here we studied how glucose exerts its effect on TXNIP gene expression via modulation of histone acetylation marks. To achieve this, we applied clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas9) to knock out histone acetyltransferase (HAT) p300 in a rat pancreatic beta cell line INS1 832/13...
October 29, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27968730/the-functionality-and-evolution-of-eukaryotic-transcriptional-enhancers
#17
A D Buffry, C C Mendes, A P McGregor
Enhancers regulate precise spatial and temporal patterns of gene expression in eukaryotes and, moreover, evolutionary changes in these modular cis-regulatory elements may represent the predominant genetic basis for phenotypic evolution. Here, we review approaches to identify and functionally analyze enhancers and their transcription factor binding sites, including assay for transposable-accessible chromatin-sequencing (ATAC-Seq) and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9, respectively...
2016: Advances in Genetics
https://www.readbyqxmd.com/read/27939672/dynamic-changes-in-chromatin-accessibility-occur-in-cd8-t-cells-responding-to-viral-infection
#18
James P Scott-Browne, Isaac F López-Moyado, Sara Trifari, Victor Wong, Lukas Chavez, Anjana Rao, Renata M Pereira
In response to acute infection, naive CD8(+) T cells expand, differentiate into effector cells, and then contract to a long-lived pool of memory cells after pathogen clearance. During chronic infections or in tumors, CD8(+) T cells acquire an "exhausted" phenotype. Here we present genome-wide comparisons of chromatin accessibility and gene expression from endogenous CD8(+) T cells responding to acute and chronic viral infection using ATAC-seq and RNA-seq techniques. Acquisition of effector, memory, or exhausted phenotypes was associated with stable changes in chromatin accessibility away from the naive T cell state...
December 20, 2016: Immunity
https://www.readbyqxmd.com/read/27936378/genome-wide-identification-of-neuronal-activity-regulated-genes-in-drosophila
#19
Xiao Chen, Reazur Rahman, Fang Guo, Michael Rosbash
Activity-regulated genes (ARGs) are important for neuronal functions like long-term memory and are well-characterized in mammals but poorly studied in other model organisms like Drosophila. Here we stimulated fly neurons with different paradigms and identified ARGs using high-throughput sequencing from brains as well as from sorted neurons: they included a narrow set of circadian neurons as well as dopaminergic neurons. Surprisingly, many ARGs are specific to the stimulation paradigm and very specific to neuron type...
December 9, 2016: ELife
https://www.readbyqxmd.com/read/27911843/impact-of-the-gut-microbiota-on-enhancer-accessibility-in-gut-intraepithelial-lymphocytes
#20
Nicholas P Semenkovich, Joseph D Planer, Philip P Ahern, Nicholas W Griffin, Charles Y Lin, Jeffrey I Gordon
The gut microbiota impacts many aspects of host biology including immune function. One hypothesis is that microbial communities induce epigenetic changes with accompanying alterations in chromatin accessibility, providing a mechanism that allows a community to have sustained host effects even in the face of its structural or functional variation. We used Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) to define chromatin accessibility in predicted enhancer regions of intestinal αβ(+) and γδ(+) intraepithelial lymphocytes purified from germ-free mice, their conventionally raised (CONV-R) counterparts, and mice reared germ free and then colonized with CONV-R gut microbiota at the end of the suckling-weaning transition...
December 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
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