Identification of gene specific cis-regulatory elements during differentiation of mouse embryonic stem cells: An integrative approach using high-throughput datasets
| العنوان: | Identification of gene specific cis-regulatory elements during differentiation of mouse embryonic stem cells: An integrative approach using high-throughput datasets |
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| المؤلفون: | Fatin N. Zainul Abidin, David R. Westhead, Salam A. Assi, Rebecca Hannah, Constanze Bonifer, Debbie K. Goode, Nadine Obier, Georges Lacaud, M. S. Vijayabaskar, Amber M L Emmett, Nisar A. Shar, Monika Lichtinger, Valerie Kouskoff, Berthold Göttgens, Michael Lie-A-Ling |
| المساهمون: | Emmett, Amber ML [0000-0003-3894-3453], Abidin, Fatin N Zainul [0000-0001-7296-3752], Hannah, Rebecca [0000-0003-0477-7792], Gottgens, Berthold [0000-0001-6302-5705], Lacaud, Georges [0000-0002-5630-2417], Westhead, David R [0000-0002-0519-3820], Apollo - University of Cambridge Repository |
| المصدر: | PLoS Computational Biology PLoS Computational Biology, Vol 15, Iss 11, p e1007337 (2019) Vijayabaskar, M S, Goode, D K, Obier, N, Lichtinger, M, Emmett, A M L, Abidin, F N Z, Shar, N, Hannah, R, Assi, S A, Lie-A-Ling, M, Gottgens, B, Lacaud, G, Kouskoff, V, Bonifer, C & Westhead, D R 2019, ' Identification of gene specific cis-regulatory elements during differentiation of mouse embryonic stem cells : An integrative approach using high-throughput datasets ', PLoS computational biology, vol. 15, no. 11, pp. e1007337 . https://doi.org/10.1371/journal.pcbi.1007337Test |
| بيانات النشر: | Public Library of Science, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Epigenomics, Gene Expression, Regulatory Sequences, Nucleic Acid, Biochemistry, Epigenesis, Genetic, Mice, 0302 clinical medicine, Mathematical and Statistical Techniques, Databases, Genetic, Transcriptional regulation, High-Throughput Screening Assays/methods, Mouse Embryonic Stem Cells/metabolism, Myocytes, Cardiac, Regulatory Elements, Transcriptional, Biology (General), Promoter Regions, Genetic, Regulation of gene expression, 0303 health sciences, Genome, Manchester Cancer Research Centre, Ecology, Chromosome Biology, Transcriptional Control, Statistics, Cell Differentiation, Mouse Embryonic Stem Cells, Myocytes, Cardiac/metabolism, Genomics, Chromatin, Computational Theory and Mathematics, Regulatory sequence, Modeling and Simulation, Physical Sciences, Epigenetics, Research Article, QH301-705.5, Gene prediction, Cell Differentiation/genetics, DNA transcription, Computational biology, Biology, Research and Analysis Methods, Gene Expression Regulation/genetics, Chromatin/metabolism, 03 medical and health sciences, Cellular and Molecular Neuroscience, Macrophages/metabolism, DNA-binding proteins, Genetics, Animals, Transcription Factors/metabolism, Gene Regulation, Statistical Methods, Gene Prediction, Molecular Biology, Transcription factor, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, ResearchInstitutes_Networks_Beacons/mcrc, Macrophages, Biology and Life Sciences, Proteins, Computational Biology, Cell Biology, Genome Analysis, Regulatory Proteins, High-Throughput Screening Assays, Gene Expression Regulation, Regulatory Elements, Transcriptional/genetics, 030217 neurology & neurosurgery, Mathematics, Transcription Factors, Forecasting |
| الوصف: | Gene expression governs cell fate, and is regulated via a complex interplay of transcription factors and molecules that change chromatin structure. Advances in sequencing-based assays have enabled investigation of these processes genome-wide, leading to large datasets that combine information on the dynamics of gene expression, transcription factor binding and chromatin structure as cells differentiate. While numerous studies focus on the effects of these features on broader gene regulation, less work has been done on the mechanisms of gene-specific transcriptional control. In this study, we have focussed on the latter by integrating gene expression data for the in vitro differentiation of murine ES cells to macrophages and cardiomyocytes, with dynamic data on chromatin structure, epigenetics and transcription factor binding. Combining a novel strategy to identify communities of related control elements with a penalized regression approach, we developed individual models to identify the potential control elements predictive of the expression of each gene. Our models were compared to an existing method and evaluated using the existing literature and new experimental data from embryonic stem cell differentiation reporter assays. Our method is able to identify transcriptional control elements in a gene specific manner that reflect known regulatory relationships and to generate useful hypotheses for further testing. Author summary The inherited information in our DNA genomes is a code which defines both the functional units (proteins, nucleic acids etc.), and patterns of their usage, necessary to make life. The genome in mammals, such as man and mouse, has genes which code for about 20000 different proteins, but the usage of these proteins differs in each different type of cell within these complex multicellular organisms. How this differential usage is controlled in known as genetic regulation, and that is what we study here. We know that the details lie in how genes are turned on and off, but until the advent of high-throughput sequencing technology a genome-wide study was nearly impossible. Further complicating our efforts to understand genetic regulation is the involvement of parts of the genome that were previously deemed junk. In this work, we have focussed on how the genes are controlled at various developmental stages in mouse, by looking at the sequencing data from different regulatory mechanisms such as protein binding and local changes to DNA packaging etc. On a gene-by-gene basis, we have built statistical models that predict how genes are controlled when cells develop. These predictions provide a focus for future experimental studies of genetic regulation. |
| وصف الملف: | application/pdf; application/octet-stream |
| اللغة: | English |
| تدمد: | 1553-7358 1553-734X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ad63bce7b85c00e7164b22b42317509eTest http://europepmc.org/articles/PMC6855567Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ad63bce7b85c00e7164b22b42317509e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537358 1553734X |
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