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cis-regulatory elements

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https://www.readbyqxmd.com/read/28219948/genomic-integration-of-wnt-%C3%AE-catenin-and-bmp-smad1-signaling-coordinates-foregut-and-hindgut-transcriptional-program
#1
Mariana L Stevens, Praneet Chaturvedi, Scott A Rankin, Melissa Macdonald, Sajjeev Jagannathan, Masashi Yukawa, Artem Barski, Aaron M Zorn
Digestive system development is orchestrated by combinatorial signaling interactions between endoderm and mesoderm, but how these signals are integrated in the genome is poorly understood. Here we identified the transcriptomes of Xenopus foregut and hindgut progenitors, which are conserved with mammals. Using RNA-seq and ChIP-seq we show that BMP/Smad1 regulates dorsal-ventral gene expression in both the endoderm and mesoderm, whereas Wnt/β-catenin acts as a genome-wide toggle between foregut and hindgut programs...
February 20, 2017: Development
https://www.readbyqxmd.com/read/28216637/mutations-underlying-episodic-ataxia-type-1-antagonize-kv1-1-rna-editing
#2
Elizabeth A Ferrick-Kiddie, Joshua J C Rosenthal, Gregory D Ayers, Ronald B Emeson
Adenosine-to-inosine RNA editing in transcripts encoding the voltage-gated potassium channel Kv1.1 converts an isoleucine to valine codon for amino acid 400, speeding channel recovery from inactivation. Numerous Kv1.1 mutations have been associated with the human disorder Episodic Ataxia Type-1 (EA1), characterized by stress-induced ataxia, myokymia, and increased prevalence of seizures. Three EA1 mutations, V404I, I407M, and V408A, are located within the RNA duplex structure required for RNA editing. Each mutation decreased RNA editing both in vitro and using an in vivo mouse model bearing the V408A allele...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28216629/matrix-attachment-region-combinations-increase-transgene-expression-in-transfected-chinese-hamster-ovary-cells
#3
Chun-Peng Zhao, Xiao Guo, Si-Jia Chen, Chang-Zheng Li, Yun Yang, Jun-He Zhang, Shao-Nan Chen, Yan-Long Jia, Tian-Yun Wang
Matrix attachment regions (MARs) are cis-acting DNA elements that can increase transgene expression levels in a CHO cell expression system. To investigate the effects of MAR combinations on transgene expression and the underlying regulatory mechanisms, we generated constructs in which the enhanced green fluorescent protein (eGFP) gene flanked by different combinations of human β-interferon and β-globin MAR (iMAR and gMAR, respectively), which was driven by the cytomegalovirus (CMV) or simian virus (SV) 40 promoter...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28203648/gene-regulatory-effects-of-disease-associated-variation-in-the-nrf2-network
#4
Sarah E Lacher, Matthew Slattery
Reactive oxygen species (ROS), which are both a natural byproduct of oxidative metabolism and an undesirable byproduct of many environmental stressors, can damage all classes of cellular macromolecules and promote diseases from cancer to neurodegeneration. The actions of ROS are mitigated by the transcription factor NRF2, which regulates expression of antioxidant genes via its interaction with cis-regulatory antioxidant response elements (AREs). However, despite the seemingly straightforward relationship between the opposing forces of ROS and NRF2, regulatory precision in the NRF2 network is essential...
December 2016: Curr Opin Toxicol
https://www.readbyqxmd.com/read/28193859/genetic-regulatory-signatures-underlying-islet-gene-expression-and-type-2-diabetes
#5
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/28193687/rainbow-enhancers-regulate-restrictive-transcription-in-teleost-green-red-and-blue-cones
#6
Wei Fang, Chuanyu Guo, Xiangyun Wei
Photoreceptor-specific transcription of individual genes collectively constitutes the transcriptional profile that orchestrates the structural and functional characteristics of each photoreceptor type. It is challenging, however, to study the transcriptional specificity of individual photoreceptor genes because each gene's distinct spatiotemporal transcription patterns are determined by the unique interactions between a specific set of transcription factors and the gene's own cis-regulatory elements (CREs), which remain unknown for most of the genes...
February 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28192796/analysis-of-the-prpf31-gene-in-spanish-autosomal-dominant-retinitis-pigmentosa-patients-a-novel-genomic-rearrangement
#7
Inmaculada Martin-Merida, Rocio Sanchez-Alcudia, Patricia Fernandez-San Jose, Fiona Blanco-Kelly, Raquel Perez-Carro, Luciana Rodriguez-Jacy da Silva, Berta Almoguera, Blanca Garcia-Sandoval, Maria Isabel Lopez-Molina, Almudena Avila-Fernandez, Miguel Carballo, Marta Corton, Carmen Ayuso
Purpose: The aim was to determine the prevalence of PRPF31 mutations in a cohort of Spanish autosomal dominant retinitis pigmentosa (adRP) families to deepen knowledge of the pathogenic mechanisms underlying the disease and to assess genotype-phenotype correlations. Methods: A cohort of 211 adRP patients was screened for variants in PRPF31 by using a combined strategy comprising next-generation sequencing approaches and copy-number variation (CNV) analysis. Quantitative RT-PCR and CNV analysis of the regulatory MSR1 element were also performed to assess PRPF31 gene expression...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28179496/cutting-edge-chromatin-accessibility-programs-cd8-t-cell-memory
#8
Christopher D Scharer, Alexander P R Bally, Bhanu Gandham, Jeremy M Boss
CD8 T cell memory is characterized by rapid recall of effector function, increased proliferation, and reduced activation requirements. Despite the extensive functional characterization, the molecular mechanisms that facilitate these enhanced properties are not well characterized. In this study, the assay for transposase-accessible chromatin sequencing was employed to map the cis-regulatory elements in CD8 T cells responding to acute and chronic lymphocytic choriomeningitis virus infections. Integration of chromatin accessibility profiles with gene expression data identified unique regulatory modules that were enriched for distinct combinations of transcription factor-binding motifs...
February 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28178571/genome-wide-identification-and-analysis-of-biotic-and-abiotic-stress-regulation-of-small-heat-shock-protein-hsp20-family-genes-in-bread-wheat
#9
Senthilkumar K Muthusamy, Monika Dalal, Viswanathan Chinnusamy, Kailash C Bansal
Small Heat Shock Proteins (sHSPs)/HSP20 are molecular chaperones that protect plants by preventing protein aggregation during abiotic stress conditions, especially heat stress. Due to global climate change, high temperature is emerging as a major threat to wheat productivity. Thus, the identification of HSP20 and analysis of HSP transcriptional regulation under different abiotic stresses in wheat would help in understanding the role of these proteins in abiotic stress tolerance. We used sequences of known rice and Arabidopsis HSP20 HMM profiles as queries against publicly available wheat genome and wheat full length cDNA databases (TriFLDB) to identify the respective orthologues from wheat...
January 22, 2017: Journal of Plant Physiology
https://www.readbyqxmd.com/read/28176764/foxn1-%C3%AE-5t-transcriptional-axis-controls-cd8-t-cell-production-in-the-thymus
#10
Muhammad Myn Uddin, Izumi Ohigashi, Ryo Motosugi, Tomomi Nakayama, Mie Sakata, Jun Hamazaki, Yasumasa Nishito, Immanuel Rode, Keiji Tanaka, Tatsuya Takemoto, Shigeo Murata, Yousuke Takahama
The thymus is an organ that produces functionally competent T cells that protect us from pathogens and malignancies. Foxn1 is a transcription factor that is essential for thymus organogenesis; however, the direct target for Foxn1 to actuate thymic T-cell production is unknown. Here we show that a Foxn1-binding cis-regulatory element promotes the transcription of β5t, which has an essential role in cortical thymic epithelial cells to induce positive selection of functionally competent CD8(+) T cells. A point mutation in this genome element results in a defect in β5t expression and CD8(+) T-cell production in mice...
February 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28176760/dogmp1-from-dendrobium-officinale-contributes-to-mannose-content-of-water-soluble-polysaccharides-and-plays-a-role-in-salt-stress-response
#11
Chunmei He, Zhenming Yu, Jaime A Teixeira da Silva, Jianxia Zhang, Xuncheng Liu, Xiaojuan Wang, Xinhua Zhang, Songjun Zeng, Kunlin Wu, Jianwen Tan, Guohua Ma, Jianping Luo, Jun Duan
GDP-mannose pyrophosphorylase (GMP) catalyzed the formation of GDP-mannose, which serves as a donor for the biosynthesis of mannose-containing polysaccharides. In this study, three GMP genes from Dendrobium officinale (i.e., DoGMPs) were cloned and analyzed. The putative 1000 bp upstream regulatory region of these DoGMPs was isolated and cis-elements were identified, which indicates their possible role in responses to abiotic stresses. The DoGMP1 protein was shown to be localized in the cytoplasm. To further study the function of the DoGMP1 gene, 35S:DoGMP1 transgenic A...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28174576/comparative-analysis-of-agpase-genes-and-encoded-proteins-in-eight-monocots-and-three-dicots-with-emphasis-on-wheat
#12
Ritu Batra, Gautam Saripalli, Amita Mohan, Saurabh Gupta, Kulvinder S Gill, Pritish K Varadwaj, Harindra S Balyan, Pushpendra K Gupta
ADP-glucose pyrophosphorylase (AGPase) is a heterotetrameric enzyme with two large subunits (LS) and two small subunits (SS). It plays a critical role in starch biosynthesis. We are reporting here detailed structure, function and evolution of the genes encoding the LS and the SS among monocots and dicots. "True" orthologs of maize Sh2 (AGPase LS) and Bt2 (AGPase SS) were identified in seven other monocots and three dicots; structure of the enzyme at protein level was also studied. Novel findings of the current study include the following: (i) at the DNA level, the genes controlling the SS are more conserved than those controlling the LS; the variation in both is mainly due to intron number, intron length and intron phase distribution; (ii) at protein level, the SS genes are more conserved relative to those for LS; (iii) "QTCL" motif present in SS showed evolutionary differences in AGPase belonging to wheat 7BS, T...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28174238/functional-characterisation-of-cis-regulatory-elements-governing-dynamic-eomes-expression-in-the-early-mouse-embryo
#13
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/28168220/the-structurally-disordered-paramyxovirus-nucleocapsid-protein-tail-domain-is-a-regulator-of-the-mrna-transcription-gradient
#14
Robert M Cox, Stefanie A Krumm, Vidhi D Thakkar, Maximilian Sohn, Richard K Plemper
The paramyxovirus RNA-dependent RNA-polymerase (RdRp) complex loads onto the nucleocapsid protein (N)-encapsidated viral N:RNA genome for RNA synthesis. Binding of the RdRp of measles virus (MeV), a paramyxovirus archetype, is mediated through interaction with a molecular recognition element (MoRE) located near the end of the carboxyl-terminal Ntail domain. The structurally disordered central Ntail section is thought to add positional flexibility to MoRE, but the functional importance of this Ntail region for RNA polymerization is unclear...
February 2017: Science Advances
https://www.readbyqxmd.com/read/28167794/gata4-potentiates-second-heart-field-proliferation-and-hedgehog-signaling-for-cardiac-septation
#15
Lun Zhou, Jielin Liu, Menglan Xiang, Patrick Olson, Alexander Guzzetta, Ke Zhang, Ivan P Moskowitz, Linglin Xie
GATA4, an essential cardiogenic transcription factor, provides a model for dominant transcription factor mutations in human disease. Dominant GATA4 mutations cause congenital heart disease (CHD), specifically atrial and atrioventricular septal defects (ASDs and AVSDs). We found that second heart field (SHF)-specific Gata4 heterozygote embryos recapitulated the AVSDs observed in germline Gata4 heterozygote embryos. A proliferation defect of SHF atrial septum progenitors and hypoplasia of the dorsal mesenchymal protrusion, rather than anlage of the atrioventricular septum, were observed in this model...
February 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28166241/evolutionary-analysis-reveals-regulatory-and-functional-landscape-of-coding-and-non-coding-rna-editing
#16
Rui Zhang, Patricia Deng, Dionna Jacobson, Jin Billy Li
Adenosine-to-inosine RNA editing diversifies the transcriptome and promotes functional diversity, particularly in the brain. A plethora of editing sites has been recently identified; however, how they are selected and regulated and which are functionally important are largely unknown. Here we show the cis-regulation and stepwise selection of RNA editing during Drosophila evolution and pinpoint a large number of functional editing sites. We found that the establishment of editing and variation in editing levels across Drosophila species are largely explained and predicted by cis-regulatory elements...
February 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28165450/functional-roles-of-aves-class-specific-cis-regulatory-elements-on-macroevolution-of-bird-specific-features
#17
Ryohei Seki, Cai Li, Qi Fang, Shinichi Hayashi, Shiro Egawa, Jiang Hu, Luohao Xu, Hailin Pan, Mao Kondo, Tomohiko Sato, Haruka Matsubara, Namiko Kamiyama, Keiichi Kitajima, Daisuke Saito, Yang Liu, M Thomas P Gilbert, Qi Zhou, Xing Xu, Toshihiko Shiroishi, Naoki Irie, Koji Tamura, Guojie Zhang
Unlike microevolutionary processes, little is known about the genetic basis of macroevolutionary processes. One of these magnificent examples is the transition from non-avian dinosaurs to birds that has created numerous evolutionary innovations such as self-powered flight and its associated wings with flight feathers. By analysing 48 bird genomes, we identified millions of avian-specific highly conserved elements (ASHCEs) that predominantly (>99%) reside in non-coding regions. Many ASHCEs show differential histone modifications that may participate in regulation of limb development...
February 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28162085/a-novel-regulatory-element-responsible-for-high-transcriptional-expression-of-acerola-gdp-d-mannose-pyrophosphorylase-gene
#18
Takayuki Kondo, Yukichi Fujikawa, Muneharu Esaka
GDP-d-mannose pyrophosphorylase (GMP) is one of the enzymes that highly expressed in acerola plants. A promoter assay suggests the presence of a new cis-element in the -1087 to -1083 bp sequence of the MgGMP promoter. Moreover, cis-elements, present in the -1080 to -600 bp sequence of the MgGMP promoter, function as enhancers of MgGMP expression.
February 6, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28160379/spearmint-r2r3-myb-transcription-factor-msmyb-negatively-regulates-monoterpene-production-and-suppresses-the-expression-of-geranyl-diphosphate-synthase-large-subunit-msgpps-lsu
#19
Vaishnavi Amarr Reddy, Qian Wang, Niha Dhar, Nadimuthu Kumar, Prasanna Nori Venkatesh, Chakravarthy Rajan, Deepa Panicker, Vishweshwaran Sridhar, Hui-Zhu Mao, Rajani Sarojam
Many aromatic plants, like spearmint, produce valuable essential oils in specialized structures called peltate glandular trichomes (PGT). Understanding the regulatory mechanisms behind the production of these important secondary metabolites will help design new approaches to engineer them. Here, we identified a PGT-specific R2R3-MYB gene MsMYB, from comparative RNA-Seq data of spearmint, and functionally characterized it. Analysis of MsMYB-RNAi transgenic lines showed increased levels of monoterpenes and MsMYB-overexpressing lines exhibited decreased levels of monoterpenes...
February 3, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28157506/not-all-h3k4-methylations-are-created-equal-mll2-compass-dependency-in-primordial-germ-cell-specification
#20
Deqing Hu, Xin Gao, Kaixiang Cao, Marc A Morgan, Gloria Mas, Edwin R Smith, Andrew G Volk, Elizabeth T Bartom, John D Crispino, Luciano Di Croce, Ali Shilatifard
The spatiotemporal regulation of gene expression is central for cell-lineage specification during embryonic development and is achieved through the combinatorial action of transcription factors/co-factors and epigenetic states at cis-regulatory elements. Here, we show that in addition to implementing H3K4me3 at promoters of bivalent genes, Mll2 (KMT2B)/COMPASS can also implement H3K4me3 at a subset of non-TSS regulatory elements, a subset of which shares epigenetic signatures of active enhancers. Our mechanistic studies reveal that association of Mll2's CXXC domain with CpG-rich regions plays an instrumental role for chromatin targeting and subsequent implementation of H3K4me3...
February 2, 2017: Molecular Cell
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