Diermeier, Sarah ORCID: 0000-0002-6120-2744, Kolovos, Petros ORCID: 0000-0002-0787-6158, Heizinger, Leonhard ORCID: 0000-0002-9766-7471, Schwartz, Uwe, Georgomanolis, Theodore, Zirkel, Anne, Wedemann, Gero ORCID: 0000-0001-7869-774X, Grosveld, Frank, Knoch, Tobias A., Merkl, Rainer, Cook, Peter R., Laengst, Gernot and Papantonis, Argyris ORCID: 0000-0001-7551-1073 (2014). TNF alpha signalling primes chromatin for NF-kappa B binding and induces rapid and widespread nucleosome repositioning. Genome Biol., 15 (12). LONDON: BMC. ISSN 1474-760X

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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: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Diermeier, SarahUNSPECIFIEDorcid.org/0000-0002-6120-2744UNSPECIFIED
Kolovos, PetrosUNSPECIFIEDorcid.org/0000-0002-0787-6158UNSPECIFIED
Heizinger, LeonhardUNSPECIFIEDorcid.org/0000-0002-9766-7471UNSPECIFIED
Schwartz, UweUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Georgomanolis, TheodoreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zirkel, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wedemann, GeroUNSPECIFIEDorcid.org/0000-0001-7869-774XUNSPECIFIED
Grosveld, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knoch, Tobias A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Merkl, RainerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cook, Peter R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laengst, GernotUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Papantonis, ArgyrisUNSPECIFIEDorcid.org/0000-0001-7551-1073UNSPECIFIED
URN: urn:nbn:de:hbz:38-452180
DOI: 10.1186/s13059-014-0536-6
Journal or Publication Title: Genome Biol.
Volume: 15
Number: 12
Date: 2014
Publisher: BMC
Place of Publication: LONDON
ISSN: 1474-760X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CHROMOSOME CONFORMATION CAPTURE; GENOMIC INTERACTIONS; REGULATORY ELEMENTS; ALU ELEMENTS; HUMAN GENES; HUMAN-CELLS; TRANSCRIPTION; ENHANCERS; SEQUENCE; DYNAMICSMultiple languages
Biotechnology & Applied Microbiology; Genetics & HeredityMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/45218

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