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ChIP-seq OR RNA-seq

Burak Tepe, Matthew C Hill, Brandon T Pekarek, Patrick J Hunt, Thomas J Martin, James F Martin, Benjamin R Arenkiel
Cellular heterogeneity within the mammalian brain poses a challenge toward understanding its complex functions. Within the olfactory bulb, odor information is processed by subtypes of inhibitory interneurons whose heterogeneity and functionality are influenced by ongoing adult neurogenesis. To investigate this cellular heterogeneity and better understand adult-born neuron development, we utilized single-cell RNA sequencing and computational modeling to reveal diverse and transcriptionally distinct neuronal and nonneuronal cell types...
December 4, 2018: Cell Reports
Su Yang, Shihua Li, Xiao-Jiang Li
Virus-mediated expression of CRISPR/Cas9 is commonly used for genome editing in animal brains to model or treat neurological diseases, but the potential neurotoxicity of overexpressing bacterial Cas9 in the mammalian brain remains unknown. Through RNA sequencing (RNA-seq) analysis, we find that virus-mediated expression of Cas9 influences the expression of genes involved in neuronal functions. Reducing the half-life of Cas9 by tagging with geminin, whose expression is regulated by the cell cycle, maintains the genome editing capacity of Cas9 but significantly alleviates neurotoxicity...
December 4, 2018: Cell Reports
Marius Gheorghe, Geir Kjetil Sandve, Aziz Khan, Jeanne Chèneby, Benoit Ballester, Anthony Mathelier
Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is the most popular assay to identify genomic regions, called ChIP-seq peaks, that are bound in vivo by transcription factors (TFs). These regions are derived from direct TF-DNA interactions, indirect binding of the TF to the DNA (through a co-binding partner), nonspecific binding to the DNA, and noise/bias/artifacts. Delineating the bona fide direct TF-DNA interactions within the ChIP-seq peaks remains challenging. We developed a dedicated software, ChIP-eat, that combines computational TF binding models and ChIP-seq peaks to automatically predict direct TF-DNA interactions...
December 4, 2018: Nucleic Acids Research
Dmitry Sutormin, Natalia Rubanova, Maria Logacheva, Dmitry Ghilarov, Konstantin Severinov
An important antibiotic target, DNA gyrase is an essential bacterial enzyme that introduces negative supercoils into DNA and relaxes positive supercoils accumulating in front of moving DNA and RNA polymerases. By altering the superhelical density, gyrase may regulate expression of bacterial genes. The information about how gyrase is distributed along genomic DNA and whether its distribution is affected by drugs is scarce. During catalysis, gyrase cleaves both DNA strands forming a covalently bound intermediate...
December 4, 2018: Nucleic Acids Research
Takafumi Kawamura, Masayoshi Yamamoto, Katsunori Suzuki, Yuhi Suzuki, Megumu Kamishima, Mayu Sakata, Kiyotaka Kurachi, Mitsutoshi Setoh, Hiroyuki Konno, Hiroya Takeuchi
Background: Colitis-associated cancer (CAC) is one of the prognostic factors in inflammatory bowel disease (IBD), and prevention of CAC is a critical concern for patients with IBD. Component cells of the microenvironment, especially myofibroblasts, are known to affect tumor development, but the role of intestinal myofibroblasts (IMFs) in CAC has not been clarified. Here, we explored the role of IMFs in CAC and sought to identify candidate genes as novel therapeutic targets for the prevention of CAC...
December 4, 2018: Inflammatory Bowel Diseases
Indu Warrier, Nikhil Ram-Mohan, Zeyu Zhu, Ariana Hazery, Haley Echlin, Jason Rosch, Michelle M Meyer, Tim van Opijnen
Efficient and highly organized regulation of transcription is fundamental to an organism's ability to survive, proliferate, and quickly respond to its environment. Therefore, precise mapping of transcriptional units and understanding their regulation is crucial to determining how pathogenic bacteria cause disease and how they may be inhibited. In this study, we map the transcriptional landscape of the bacterial pathogen Streptococcus pneumoniae TIGR4 by applying a combination of high-throughput RNA-sequencing techniques...
December 5, 2018: PLoS Pathogens
Ying Yao, Asima Zia, Łukasz Wyrożemski, Ida Lindeman, Geir Kjetil Sandve, Shuo-Wang Qiao
By offering high sequencing speed and ultra-high-throughput at a low price, Illumina next-generation sequencing platforms have been widely adopted in recent years. However, an experiment with multiplexed library could be at risk of molecular recombination, known as "index switching", which causes a proportion of the reads to be assigned to an incorrect sample. It is reported that a new advance, exclusion amplification (ExAmp) in conjunction with the patterned flow cell technology introduced on HiSeq 3000/HiSeq 4000/HiSeq X sequencing systems, potentially suffers from a higher rate of index switching than conventional bridge amplification...
2018: PloS One
Jibin Zhang, Carl J Schmidt, Susan J Lamont
Modern fast-growing broilers are susceptible to cardiac dysfunctions because their relatively small hearts cannot adequately meet the increased need of pumping blood through a large body mass. To improve cardiac health in broilers through breeding, we need to identify the genes and pathways that contribute to imbalanced cardiac development and occurrence of heart dysfunction. Two broiler lines-Ross 708 and Illinois-were included in this study as models of modern fast-growing and heritage slow-growing broilers, respectively...
2018: PloS One
Cheuk-Ting Law, Lai Wei, Felice Ho-Ching Tsang, Cerise Yuen-Ki Chan, Iris Ming-Jing Xu, Robin Kit-Ho Lai, Daniel Wai-Hung Ho, Joyce Man-Fong Lee, Carmen Chak-Lui Wong, Irene Oi-Lin Ng, Chun-Ming Wong
Hepatocellular carcinoma (HCC) is the third lethal cancer worldwide. Increasing evidence showed that epigenetic alterations play an important role in human carcinogenesis. Deregulation of DNA methylation and histone modifications have recently been characterized in HCC, but the significance of chromatin remodeling in liver carcinogenesis remains to be explored. In this study, by systematically analyzing the expression of chromatin remodeling genes in human HCCs, we found that HELicase, Lymphoid-Specific (HELLS), a SWI2/SNF2 chromatin remodeling enzyme, was remarkably overexpressed in HCC...
December 5, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Brett McGettigan, Rachel McMahan, David Orlicky, Matthew Burchill, Thomas Danhorn, Prashanth Francis, Lin Ling Cheng, Lucy Golden-Mason, Claudia Jakubzick, Hugo Rosen
A crucial component of non-alcoholic fatty liver disease (NAFLD) pathogenesis is lipid stress, which may contribute to hepatic inflammation and activation of innate immunity in the liver. However, little is known regarding how dietary lipids, including fat and cholesterol, may facilitate innate immune activation in vivo. We hypothesized that dietary fat and cholesterol drive NAFLD progression to steatohepatitis and hepatic fibrosis by altering the transcription and phenotype of hepatic macrophages METHODS: This hypothesis was tested by using RNA-seq methods to characterize and analyze sort-purified hepatic macrophage populations that were isolated from mice fed diets with varying amounts of fat and cholesterol RESULTS: The addition of cholesterol to a high fat diet triggered hepatic pathology reminiscent of advanced non-alcoholic steatohepatitis (NASH) in humans characterized by signs of cholesterol dysregulation, generation of oxidized LDL, increased recruitment of hepatic macrophages, and significant fibrosis...
December 5, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Lori L O'Brien, Alexander N Combes, Kieran M Short, Nils O Lindström, Peter H Whitney, Luise A Cullen-McEwen, Adler Ju, Ahmed Abdelhalim, Odyssé Michos, John F Bertram, Ian M Smyth, Melissa H Little, Andrew P McMahon
A normal endowment of nephrons in the mammalian kidney requires a balance of nephron progenitor self-renewal and differentiation throughout development. Here, we provide evidence for a novel action of ureteric branch tip-derived Wnt11 in progenitor cell organization and interactions within the nephrogenic niche, ultimately determining nephron endowment. In Wnt11 mutants, nephron progenitors dispersed from their restricted niche, intermixing with interstitial progenitors. Nephron progenitor differentiation was accelerated, kidneys were significantly smaller, and the nephron progenitor pool was prematurely exhausted, halving the final nephron count...
December 5, 2018: ELife
Hao Li, Haochen Xu, Hongyan Wen, Tianlong Liu, Yingying Sun, Ning Xiao, Congxia Bai, Jing Ge, Xuliang Wang, Li Song, Yan Song, Yinhui Zhang, Jingzhou Chen
Hypertensive intracerebral hemorrhage (ICH) is a devastating cerebrovascular disease with no effective treatment. Lysyl hydroxylase 3 (LH3) is essential for collagen IV intermolecular crosslinking and stabilization. Deficiency in LH3 affects the assembly and secretion of collagen IV and basement membrane (BM) integrity of vessels. Here, we investigated whether LH3 has significant implications for disease progression and therapeutic intervention. Spontaneous hypertensive ICH of mice was induced by angiotensin II and L-NAME treatment...
December 5, 2018: Journal of Cerebral Blood Flow and Metabolism
Viswanath Gunda, Benjamin Gigliotti, Tameem Ashry, Dorothy Ndishabandi, Michael McCarthy, Zhiheng Zhou, Salma Amin, Kyu Eun Lee, Tabea Stork, Lori Wirth, Gordon J Freeman, Alessandro Alessandrini, Sareh Parangi
Patients with anaplastic thyroid cancer (ATC) have an extremely poor prognosis despite multimodal therapy with surgery and chemoradiation. Lenvatinib, a multi-targeted tyrosine kinase inhibitor, and checkpoint inhibitors targeting the programmed cell death pathway have proven effective in some patients with advanced thyroid cancer. Combination of these therapies is a potential means to boost effectiveness and minimize treatment resistance in ATC. We utilized our novel immunocompetent murine model of orthotopic ATC to demonstrate that lenvatinib led to significant tumor shrinkage and increased survival, while combination therapy led to dramatic improvements in both...
December 4, 2018: International Journal of Cancer. Journal International du Cancer
Syed Shoeb Razvi, Hani Choudhry, Mohammed Nihal Hasan, Mohammed A Hassan, Said Salama Moselhy, Khalid Omer Abualnaja, Mazin A Zamzami, Taha Abduallah Kumosani, Abdulrahman Labeed Al-Malki, Majed A Halwani, Abdulkhaleg Ibrahim, Ali Hamiche, Christian Bronner, Tadao Asami, Mahmoud Alhosin
Natural polyamines such as putrescine, spermidine, and spermine are crucial in the cell proliferation and maintenance in all the eukaryotes. However, the requirement of polyamines in tumor cells is stepped up to maintain tumorigenicity. Many synthetic polyamine analogues have been designed recently to target the polyamine metabolism in tumors to induce apoptosis. N4 -Erucoyl spermidine (designed as N4 -Eru), a novel acylspermidine derivative, has been shown to exert selective inhibitory effects on both hematological and solid tumors, but its mechanisms of action are unknown...
2018: Epigenetics insights
Hongbo Zhao, Yutang Huang, Jingjing Shi, Yi Dai, Lanxiang Wu, Honghao Zhou
Gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (EGFR-TKI), is used clinically as first-line therapy in patients with advanced non-small cell lung cancer (NSCLC) with EGFR activating mutations, but the inevitable development of acquired resistance limits its efficacy. In up to 30-40% of NSCLC cases, the mechanism underlying acquired resistance remains unknown. ATP-binding cassette (ABC) transporters are a family of membrane proteins that can significantly influence the bioavailability of numerous drugs, and have confirmed to play an essential role in multidrug resistance (MDR) in cancer chemotherapy...
2018: Frontiers in Pharmacology
Rong Wu, Ang Li, Baofa Sun, Jian-Guang Sun, Jinhua Zhang, Ting Zhang, Yusheng Chen, Yujie Xiao, Yuhao Gao, Qingyang Zhang, Jun Ma, Xin Yang, Yajin Liao, Wei-Yi Lai, Xiaolong Qi, Shukun Wang, Yousheng Shu, Hai-Lin Wang, Fengchao Wang, Yun-Gui Yang, Zengqiang Yuan
While N6 -methyladenosine (m6 A), the most abundant internal modification in eukaryotic mRNA, is linked to cell differentiation and tissue development, the biological significance of m6 A modification in mammalian glial development remains unknown. Here, we identify a novel m6 A reader, Prrc2a (Proline rich coiled-coil 2 A), which controls oligodendrocyte specification and myelination. Nestin-Cre-mediated knockout of Prrc2a induces significant hypomyelination, decreased lifespan, as well as locomotive and cognitive defects in a mouse model...
December 4, 2018: Cell Research
Rodgoun Attarian, Guanggan Hu, Eddy Sánchez-León, Mélissa Caza, Daniel Croll, Eunsoo Do, Horacio Bach, Tricia Missall, Jennifer Lodge, Won Hee Jung, James W Kronstad
The acquisition of iron and the maintenance of iron homeostasis are important aspects of virulence for the pathogenic fungus Cryptococcus neoformans In this study, we characterized the role of the monothiol glutaredoxin Grx4 in iron homeostasis and virulence in C. neoformans Monothiol glutaredoxins are important regulators of iron homeostasis because of their conserved roles in [2Fe-2S] cluster sensing and trafficking. We initially identified Grx4 as a binding partner of Cir1, a master regulator of iron-responsive genes and virulence factor elaboration in C...
December 4, 2018: MBio
Mi-Jin An, Dae-Hyun Kim, Chul-Hong Kim, Mijin Kim, Sangmyung Rhee, Sang-Beom Seo, Jung-Woong Kim
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most lethal cancer worldwide. Although gene mutations associated with HCC development have been intensively studied, how epigenetic factors specifically modulate the functional properties of HCC by regulating target gene expression is unclear. Here we demonstrated the overexpression of KDM3B in liver tissue of HCC patients using public RNA-seq data. Ablation of KDM3B by CRISPR/Cas9 retarded the cell cycle and proliferation of hepatocarcinoma HepG2 cells...
December 1, 2018: Biochemical and Biophysical Research Communications
Yan Ding, Zegang Wang, Menglian Ren, Ping Zhang, Zhongnan Li, Sheng Chen, Cailin Ge, Yulong Wang
BACKGROUND: Phosphorus (Pi) deficiency induces root morphological remodeling in plants. The primary root length of rice increased under Pi deficiency stress; however, the underlying mechanism is not well understood. In this study, transcriptome analysis (RNA-seq) and Real-time quantitative PCR (qRT-PCR) techniques were combined with the determination of physiological and biochemical indexes to research the regulation mechanisms of iron (Fe) accumulation and callose deposition in rice roots, to illuminate the relationship between Fe accumulation and primary root growth under Pi deficient conditions...
December 4, 2018: BMC Plant Biology
Chunsheng Li, Ying Xu, Laihao Li, Xianqing Yang, Yueqi Wang
The toxicity of cadmium (Cd) is the major limitation to its removal using microorganisms. The Cd tolerance of Pichia kudriavzevii was obviously enhanced by acid stress based on multi-stress cross-protection. RNA-Seq showed that most differentially expressed genes (DEGs) in the Pentose phosphate pathway, Citrate cycle (TCA cycle), Glycolysis/Gluconeogenesis, Peroxisome and Glutathione metabolism were up-regulated by acid stress. The up-regulated expression of genes related to ATP synthesis (GOR1, ALD5, ADH4, ADH6, MDH2, IDH1, IDH2, and ATP19) and Cd transport (GSTY2, GTO2, GLO2, and YOR1), and the improvement of intracellular GSH level and GST activity, reduced the Cd toxicity towards P...
November 27, 2018: Journal of Hazardous Materials
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