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cis regulatory element

John Rivera, Soile V E Keränen, Steven M Gallo, Marc S Halfon
The REDfly database provides a comprehensive curation of experimentally-validated Drosophila transcriptional cis-regulatory elements and includes information on DNA sequence, experimental evidence, patterns of regulated gene expression, and more. Now in its thirteenth year, REDfly has grown to over 23 000 records of tested reporter gene constructs and 2200 tested transcription factor binding sites. Recent developments include the start of curation of predicted cis-regulatory modules in addition to experimentally-verified ones, improved search and filtering, and increased interaction with the authors of curated papers...
October 17, 2018: Nucleic Acids Research
Hiroko Kawakami, Austin Johnson, Yu Fujita, Avery Swearer, Naoyuki Wada, Yasuhiko Kawakami
BACKGROUND: Fgf10 is expressed in various tissues and organs, such as the limb bud, heart, inner ear and head mesenchyme. Previous studies identified Fgf10 enhancers for the inner ear and heart. However, Fgf10 enhancers for other tissues have not been identified. RESULTS: By using primary culture chick embryo lateral plate mesoderm cells, we compared activities of deletion constructs of the Fgf10 promoter region, cloned into a promoter-less luciferase reporter vector...
October 16, 2018: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Jon D Larson, Suzanne J Baker
To maximize the physiological relevance of in vivo brain tumor mouse models designed to study the downstream effects of oncogenic mutations, it is important to express the mutated genes at appropriate levels, in relevant cell types, and in the proper developmental context. For recurrent mutations found in the heterozygous state in tumors, expression of the mutation from the endogenous locus is a more physiologically relevant recapitulation of the brain tumor genome. Here, we describe an approach to generate knock-in mice with an inducible mutation recombined into the endogenous locus...
2019: Methods in Molecular Biology
Alexandra Ulin, Jake Henderson, Minh-Tam Pham, James Meyo, Yuying Chen, Sibel I Karchner, Jared V Goldstone, Mark E Hahn, Larissa M Williams
Interactions between regulatory pathways allow organisms to adapt to their environment and respond to stress. One interaction that has been recently identified occurs between the aryl hydrocarbon receptor (AHR) and the nuclear factor erythroid-2 related factor (NRF) family. Each transcription factor regulates numerous downstream genes involved in the cellular response to toxicants and oxidative stress; they are also implicated in normal developmental pathways. The zebrafish model was used to explore the role of AHR regulation of nrf genes during development and in response to toxicant exposure...
October 13, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Orel Mizrahi, Aharon Nachshon, Alina Shitrit, Idit A Gelbart, Martina Dobesova, Shirly Brenner, Chaim Kahana, Noam Stern-Ginossar
mRNAs carry two layers of information, the genetic code and the information that dictates their post-transcriptional fate. The latter function relies on a complex interplay between cis-elements and trans-regulators, and unbiased identification of these elements is still challenging. To identify cis-elements that control gene expression, we use dimethyl sulfate (DMS) mutational profiling with sequencing and map changes in mRNA secondary structure following viral infection. Our dynamic structural data reveal a major role for ribosomes in unwinding secondary structures, which is further supported by the relationship we uncover between structure and translation efficiency...
October 5, 2018: Molecular Cell
Bethany J Madison, Kathleen A Clark, Niraja Bhachech, Peter Hollenhorst, Barbara J Graves, Simon L Currie
Many different transcription factors (TFs) regulate gene expression in a combinatorial fashion, often by binding in close proximity to each other on composite cis-regulatory DNA elements. Here we investigated how ETS TFs bind with the AP1 TFs JUN-FOS at composite DNA-binding sites. DNA-binding ability with JUN-FOS correlated with the phenotype of ETS proteins in prostate cancer. We found that the oncogenic ETS related gene (ERG) and ETS variant (ETV) 1/4/5 subfamilies co-occupy ETS-AP1 sites with JUN-FOS in vitro, whereas JUN-FOS robustly inhibited DNA binding by the tumor suppressors ETS homologous factor (EHF) and SAM pointed domain-containing ETS TF (SPDEF)...
October 12, 2018: Journal of Biological Chemistry
M Aydın Akbudak, Ertugrul Filiz, Kubra Kontbay
Biotic and abiotic stresses negatively affect fitness, biomass production, and crop yield in plants. The dehydration-responsive element-binding proteins ( DREB ) are important transcription factors (TFs), and are induced by abiotic and biotic stresses. In this study, genome-wide identification, in silico sequence, and phylogenetic analyses and expression analyses of DREB2 genes under cadmium (Cd) and salt (NaCl) stresses in sorghum ( Sorghum bicolor , Sb ) were performed. Six putative SbDREB2 genes were identified in sorghum genome and all contained AP2 domain (PF00847)...
October 2018: 3 Biotech
Jingyi Li, Shijun Shen, Jiayu Chen, Wenqiang Liu, Xiaocui Li, Qianshu Zhu, Beiying Wang, Xiaolong Chen, Li Wu, Mingzhu Wang, Liang Gu, Hong Wang, Jiqing Yin, Cizhong Jiang, Shaorong Gao
Extensive and accurate chromatin remodeling is essential during primordial germ cell (PGC) development for the perpetuation of genetic information across generations. Here, we report that distal cis-regulatory elements (CREs) marked by DNase I-hypersensitive sites (DHSs) show temporally restricted activities during mouse and human PGC development. Using DHS maps as proxy, we accurately locate the genome-wide binding sites of pluripotency transcription factors in mouse PGCs. Unexpectedly, we found that mouse female meiotic recombination hotspots can be captured by DHSs, and for the first time, we identified 12,211 recombination hotspots in mouse female PGCs...
October 10, 2018: Cell Research
Yuri S Odaka, Takahide Tohmonda, Atsushi Toyoda, Jun Aruga
Zic3 encodes a zinc finger protein essential for the development of meso-ectodermal tissues. In mammals, Zic3 has important roles in the development of neural tube, axial skeletons, left-right body axis, and in maintaining pluripotency of ES cells. Here we characterized cis-regulatory elements required for Zic3 expression. Enhancer activities of human-chicken-conserved noncoding sequences around Zic1 and Zic3 were screened using chick whole-embryo electroporation. We identified enhancers for meso-ectodermal tissues...
October 8, 2018: Scientific Reports
Jenny L Kerschner, Sujana Ghosh, Alekh Paranjapye, Wilmel R Cosme, Marie-Pierre Audrézet, Miyuki Nakakuki, Hiroshi Ishiguro, Claude Férec, Johanna Rommens, Ann Harris
It is estimated that up to 5% of cystic fibrosis transmembrane conductance regulator (CFTR) pathogenic alleles are unidentified. Some of these errors may lie in non-coding regions of the locus and impact gene expression. To identify regulatory element variants in the CFTR locus, SureSelect targeted enrichment of 460kb encompassing the gene was optimized to deep-sequence genomic DNA from 80 CF patients with an unequivocal clinical diagnosis but only one or no CFTR-coding region pathogenic variants. Bioinformatics tools were used to identify sequence variants and predict their impact, which was then assayed in transient reporter gene luciferase assays...
October 5, 2018: Journal of Molecular Diagnostics: JMD
Elena Martynova, Maxime Bouchard, Linda Musil, Ales Cvekl
BACKGROUND: The tissue-specific transcriptional programs during normal development require tight control by distal cis-regulatory elements, such as enhancers, with specific DNA sequences recognized by transcription factors, coactivators and chromatin remodeling enzymes. Gata3 is a sequence-specific DNA binding transcription factor that regulates formation of multiple tissues and organs, including inner ear, lens, mammary gland, T-cells, urogenital system, and thyroid gland. In the eye, Gata3 has a highly restricted expression domain in the posterior part of the lens vesicle; however, the underlying regulatory mechanisms are unknown...
October 8, 2018: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Johannes Braun, Sandra Fischer, Zhenjiang Z Xu, Hongying Sun, Dalia H Ghoneim, Anna T Gimbel, Uwe Plessmann, Henning Urlaub, David H Mathews, Julia E Weigand
Post-transcriptional gene regulation controls the amount of protein produced from a specific mRNA by altering both its decay and translation rates. Such regulation is primarily achieved by the interaction of trans-acting factors with cis-regulatory elements in the untranslated regions (UTRs) of mRNAs. These interactions are guided either by sequence- or structure-based recognition. Similar to sequence conservation, the evolutionary conservation of a UTR's structure thus reflects its functional importance. We used such structural conservation to identify previously unknown cis-regulatory elements...
October 8, 2018: Nucleic Acids Research
Lijuan Du, Amy Zhou, Alex Sohr, Sougata Roy
Binary transcription systems are powerful genetic tools widely used for visualizing and manipulating cell fate and gene expression in specific groups of cells or tissues in model organisms. These systems contain two components as separate transgenic lines. A driver line expresses a transcriptional activator under the control of tissue-specific promoters/enhancers, and a reporter/effector line harbors a target gene placed downstream to the binding site of the transcription activator. Animals harboring both components induce tissue-specific transactivation of a target gene expression...
September 19, 2018: Journal of Visualized Experiments: JoVE
Yina Jiang, Qiujin Xie, Wanxiao Wang, Jun Yang, Xiaowei Zhang, Nan Yu, Yun Zhou, Ertao Wang
Most land plants evolve a mutualistic symbiosis with arbuscular mycorrhizal (AM) fungi to improve nutrient acquisition from the soil. In return, up to 20% of host plant photosynthate is transferred to the mycorrhizal fungus in the form of lipids and sugar. Nutrient exchange must be regulated by both partners in order to maintain a reliable symbiotic relationship. However, the mechanisms underlying the regulation of lipid transfer from plant to AM fungus remain elusive. Here, we show that Medicago truncatula AP2/EREBP transcription factor WRI5a, and likely its two homologs WRI5b/Erf1 and WRI5c, are master regulators of AM symbiosis by controlling lipid transfer and periarbuscular membrane formation...
October 4, 2018: Molecular Plant
KaHoua Yang, Junsu Kang
Regenerative capacity is widespread throughout almost all animal phyla. However, the distribution pattern remains incompletely understood. Various examples show that very closely related species display different regenerative capacities. Why and how have diverse regenerative capacities evolved across species? One prevailing thought in the field of regeneration is that most regeneration-associated factors are evolutionarily conserved, suggesting the existence of an innate tissue regeneration ability in all species...
October 5, 2018: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Julie Plaisancié, M Tarilonte, P Ramos, C Jeanton-Scaramouche, V Gaston, H Dollfus, D Aguilera, J Kaplan, L Fares-Taie, F Blanco-Kelly, C Villaverde, C Francannet, A Goldenberg, I Arroyo, J M Rozet, C Ayuso, N Chassaing, P Calvas, M Corton
There is an increasing implication of non-coding regions in pathological processes of genetic origin. This is partly due to the emergence of sophisticated techniques that have transformed research into gene expression by allowing a more global understanding of the genome, both at the genomic, epigenomic and chromatin levels. Here, we implemented the analysis of PAX6, whose coding loss-of-function variants are mainly implied in aniridia, by studying its non-coding regions (untranslated regions, introns and cis-regulatory sequences)...
October 5, 2018: Human Genetics
Matthew Harder, Wendy Reeves, Chase Byers, Mercedes Santiago, Michael Veeman
The gene regulatory networks underlying Ciona notochord fate specification and differentiation have been extensively investigated, but the regulatory basis for regionalized expression within the notochord is not understood. Here we identify three notochord-expressed genes, C11.331, C12.115 and C8.891, with strongly enriched expression in the secondary notochord cells at the posterior tip of the tail. C11.331 and C12.115 share a distinctive expression pattern that is highly enriched in the secondary notochord lineage but also graded within that lineage with the strongest expression at the posterior tip...
October 1, 2018: Developmental Biology
Yanli Wang, Fan Song, Bo Zhang, Lijun Zhang, Jie Xu, Da Kuang, Daofeng Li, Mayank N K Choudhary, Yun Li, Ming Hu, Ross Hardison, Ting Wang, Feng Yue
Here, we introduce the 3D Genome Browser, , which allows users to conveniently explore both their own and over 300 publicly available chromatin interaction data of different types. We design a new binary data format for Hi-C data that reduces the file size by at least a magnitude and allows users to visualize chromatin interactions over millions of base pairs within seconds. Our browser provides multiple methods linking distal cis-regulatory elements with their potential target genes. Users can seamlessly integrate thousands of other omics data to gain a comprehensive view of both regulatory landscape and 3D genome structure...
October 4, 2018: Genome Biology
Yanna Xiao, Matthew B Reeves, Adam F Caulfield, Danyel Evseev, Katharine E Magor
Retinoic acid inducible gene-I (RIG-I) is a cytoplasmic RNA sensor for detecting a variety of RNA viruses including influenza A viruses. Detection ultimately produces Type I interferon (IFN), which stimulates expression of interferon stimulated genes (ISGs), including RIG-I itself in a positive feedback loop. The structure and function of RIG-I is conserved across phylogeny, despite significant protein sequence divergence, however, the promoter sequences do not show the expected phylogenetic relationships and it is not known whether they are similarly regulated...
October 1, 2018: Molecular Immunology
Chaoyang Xiong, Zengqi Wen, Juan Yu, Jun Chen, Chao-Pei Liu, Xiaodong Zhang, Ping Chen, Rui-Ming Xu, Guohong Li
BACKGROUND: H3.3 is an ancient and conserved H3 variant and plays essential roles in transcriptional regulation. HIRA complex, which is composed of HIRA, UBN1 or UBN2, and Cabin1, is a H3.3 specific chaperone complex. However, it still remains largely uncharacterized how HIRA complex specifically recognizes and deposits H3.3 to the chromatin, such as promoters and enhancers. RESULTS: In this study, we demonstrate that the UBN1 or UBN2 subunit is mainly responsible for specific recognition and direct binding of H3...
October 3, 2018: BMC Biology
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