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Nucleosome regulatory dynamics in response to TGF beta
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics. (Gyllensten)ORCID iD: 0000-0002-5056-9137
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2014 (English)In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 42, no 11, 6921-6934 p.Article in journal (Refereed) Published
Abstract [en]

Nucleosomes play important roles in a cell beyond their basal functionality in chromatin compaction. Their placement affects all steps in transcriptional regulation, from transcription factor (TF) binding to messenger ribonucleic acid (mRNA) synthesis. Careful profiling of their locations and dynamics in response to stimuli is important to further our understanding of transcriptional regulation by the state of chromatin. We measured nucleosome occupancy in human hepatic cells before and after treatment with transforming growth factor beta 1 (TGFβ1), using massively parallel sequencing. With a newly developed method, SuMMIt, for precise positioning of nucleosomes we inferred dynamics of the nucleosomal landscape. Distinct nucleosome positioning has previously been described at transcription start site and flanking TF binding sites. We found that the average pattern is present at very few sites and, in case of TF binding, the double peak surrounding the sites is just an artifact of averaging over many loci. We systematically searched for depleted nucleosomes in stimulated cells compared to unstimulated cells and identified 24 318 loci. Depending on genomic annotation, 44-78% of them were over-represented in binding motifs for TFs. Changes in binding affinity were verified for HNF4α by qPCR. Strikingly many of these loci were associated with expression changes, as measured by RNA sequencing.

Place, publisher, year, edition, pages
2014. Vol. 42, no 11, 6921-6934 p.
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Biological Sciences Medical Genetics
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URN: urn:nbn:se:uu:diva-225951DOI: 10.1093/nar/gku326ISI: 000338769400018PubMedID: 24771338OAI: oai:DiVA.org:uu-225951DiVA: diva2:722983
Note

Title also written as: Nucleosome regulatory dynamics in response to TGFβ

Available from: 2014-06-10 Created: 2014-06-10 Last updated: 2018-01-11Bibliographically approved

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Enroth, StefanWallerman, OlaHeldin, Carl-HenrikMoustakas, AristidisKomorowski, JanWadelius, Claes

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Enroth, StefanWallerman, OlaHeldin, Carl-HenrikMoustakas, AristidisKomorowski, JanWadelius, Claes
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GenomicsThe Linnaeus Centre for BioinformaticsDepartment of Immunology, Genetics and PathologyScience for Life Laboratory, SciLifeLabLudwig Institute for Cancer ResearchDepartment of Medical Biochemistry and MicrobiologyDepartment of Cell and Molecular BiologyMedical Genetics
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