Dataset Information


The activation of IL-1-induced enhancers depends on TAK1 kinase activity and NF-kappaB p65 I

ABSTRACT: The inflammatory gene response requires activation of the protein kinase TAK1, but it is currently unknown how TAK1-derived signals coordinate transcriptional programs in the genome. We determined the genome-wide binding of the TAK1-controlled NF-κB subunit p65 in relation to active enhancers and promoters of transcribed genes by ChIP-seq experiments. Out of 35,000 active enhancer regions, 410 H3K4me1-positive enhancers show interleukin (IL)-1-induced H3K27ac and p65 binding. Inhibition of TAK1, IKK2 or depletion of p65 blocked inducible enhancer activation and gene expression. As exemplified by the CXC chemokine cluster located on chromosome 4, the TAK1-p65 pathway also regulates the recruitment kinetics of the histone acetyltransferase CBP, of NF-κB p50 and of AP-1 transcription factors to both, promoters and enhancers. This study provides a high resolution view of epigenetic changes occurring during the IL-1 response and allows the first genome-wide identification of a novel class of inducible p65 NF-κB-dependent enhancers in epithelial cells. Two sets of experiments were performed as biological replicate series (rep1 and rep2) each comprising of the following 4 conditions: Human epithelial KB cells were 1) left untreated or were 2) treated with Interleukin-1-alpha (10ng/µl) for 1 hour, 3) treated for 1.5h with the TAK1 inhibitor 5Z-7-oxozeaenol (1µM) or were 4) treated with 5Z-7-oxozeaenol for 30 minutes followed by Interleukin-1-alpha for 1 hour.

ORGANISM(S): Homo sapiens  

SUBMITTER: Helmut Mueller   Heike Schneider  Lienhard Schmitz  Oliver Dittrich-Breiholz  Vera Saul  Sabin Bhuju  Liane Jurida  Marek Bartkuhn  Michael Kracht  Doris Newel  Johanna Soelch  Axel Weber  Katja Handschick 

PROVIDER: E-GEOD-64201 | ArrayExpress | 2014-12-17



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