Diermeier, Sarah and Kolovos, Petros and Heizinger, Leonhard and Schwartz, Uwe and Georgomanolis, Theodore and Zirkel, Anne and Wedemann, Gero and Grosveld, Frank and Knoch, Tobias A. and Merkl, Rainer and Cook, Peter R. and Laengst, Gernot and Papantonis, Argyris (2014) TNF alpha signalling primes chromatin for NF-kappa B binding and induces rapid and widespread nucleosome repositioning. GENOME BIOLOGY, 15 (12): 536. ISSN 1474-760X,
Full text not available from this repository. (Request a copy)Abstract
Background: The rearrangement of nucleosomes along the DNA fiber profoundly affects gene expression, but little is known about how signalling reshapes the chromatin landscape, in three-dimensional space and over time, to allow establishment of new transcriptional programs. Results: Using micrococcal nuclease treatment and high-throughput sequencing, we map genome-wide changes in nucleosome positioning in primary human endothelial cells stimulated with tumour necrosis factor alpha (TNF alpha) - a proinflammatory cytokine that signals through nuclear factor kappa-B (NF-kappa B). Within 10 min, nucleosomes reposition at regions both proximal and distal to NF-kappa B binding sites, before the transcription factor quantitatively binds thereon. Similarly, in long TNF alpha-responsive genes, repositioning precedes transcription by pioneering elongating polymerases and appears to nucleate from intragenic enhancer clusters resembling super-enhancers. By 30 min, widespread repositioning throughout megabase pair-long chromosomal segments, with consequential effects on three-dimensional structure (detected using chromosome conformation capture), is seen. Conclusions: Whilst nucleosome repositioning is viewed as a local phenomenon, our results point to effects occurring over multiple scales. Here, we present data in support of a TNF alpha-induced priming mechanism, mostly independent of NF-kappa B binding and/or elongating RNA polymerases, leading to a plastic network of interactions that affects DNA accessibility over large domains.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHROMOSOME CONFORMATION CAPTURE; GENOMIC INTERACTIONS; REGULATORY ELEMENTS; ALU ELEMENTS; HUMAN GENES; HUMAN-CELLS; TRANSCRIPTION; ENHANCERS; SEQUENCE; DYNAMICS; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Rainer Merkl Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie III |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Nov 2019 12:54 |
| Last Modified: | 28 Nov 2019 12:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/10876 |
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