4.8 Article

Nucleosome regulatory dynamics in response to TGFβ

期刊

NUCLEIC ACIDS RESEARCH
卷 42, 期 11, 页码 6921-6934

出版社

OXFORD UNIV PRESS
DOI: 10.1093/nar/gku326

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资金

  1. Swedish Research Council [521-2010-3505, 621-2011-6052]
  2. Diabetes Foundation, Sweden
  3. Ernfors Family Foundation
  4. Diabetes Wellness Network, Sverige
  5. Network of Excellence 'ENFIN', European Union [LSHG-CT-2005-518254]
  6. Polish Ministry of Science and Higher Education [N301 239536]
  7. eSSENCE Program

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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 (TGF beta 1), 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 HNF4 alpha by qPCR. Strikingly many of these loci were associated with expression changes, as measured by RNA sequencing.

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