Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Diermeier, Sarah UNSPECIFIED orcid.org/0000-0002-6120-2744 UNSPECIFIED Kolovos, Petros UNSPECIFIED orcid.org/0000-0002-0787-6158 UNSPECIFIED Heizinger, Leonhard UNSPECIFIED orcid.org/0000-0002-9766-7471 UNSPECIFIED Schwartz, Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED Georgomanolis, Theodore UNSPECIFIED UNSPECIFIED UNSPECIFIED Zirkel, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Wedemann, Gero UNSPECIFIED orcid.org/0000-0001-7869-774X UNSPECIFIED Grosveld, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Knoch, Tobias A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Merkl, Rainer UNSPECIFIED UNSPECIFIED UNSPECIFIED Cook, Peter R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Laengst, Gernot UNSPECIFIED UNSPECIFIED UNSPECIFIED Papantonis, Argyris UNSPECIFIED orcid.org/0000-0001-7551-1073 UNSPECIFIED
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:	Keywords Language CHROMOSOME CONFORMATION CAPTURE; GENOMIC INTERACTIONS; REGULATORY ELEMENTS; ALU ELEMENTS; HUMAN GENES; HUMAN-CELLS; TRANSCRIPTION; ENHANCERS; SEQUENCE; DYNAMICS Multiple languages Biotechnology & Applied Microbiology; Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/45218