title: The Activation of IL-1-Induced Enhancers Depends on TAK1 Kinase Activity and NF-κB p65.
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 chromatin immunoprecipitation sequencing (ChIP-seq) experiments. Out of 35,000 active enhancer regions, 410 H3K4me1-positive enhancers show interleukin 1 (IL-1)-induced H3K27ac and p65 binding. Inhibition of TAK1 or 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 genome-wide identification of a distinct class of inducible p65 NF-κB-dependent enhancers in epithelial cells.
authors: Rudolf-Buchheim-Institute of Pharmacology, Justus-Liebig-University Giessen, 35392 Giessen, Germany.
authors: Liane
authors: L
authors: Jurida
authors: Rudolf-Buchheim-Institute of Pharmacology, Justus-Liebig-University Giessen, 35392 Giessen, Germany.
authors: Johanna
authors: J
authors: Soelch
authors: Institute for Genetics, Justus-Liebig-University Giessen, 35392 Giessen, Germany.
authors: Marek
authors: M
authors: Bartkuhn
authors: Rudolf-Buchheim-Institute of Pharmacology, Justus-Liebig-University Giessen, 35392 Giessen, Germany.
authors: Katja
authors: K
authors: Handschick
authors: Rudolf-Buchheim-Institute of Pharmacology, Justus-Liebig-University Giessen, 35392 Giessen, Germany.
authors: Helmut
authors: H
authors: Müller
authors: Rudolf-Buchheim-Institute of Pharmacology, Justus-Liebig-University Giessen, 35392 Giessen, Germany.
authors: Doris
authors: D
authors: Newel
authors: Rudolf-Buchheim-Institute of Pharmacology, Justus-Liebig-University Giessen, 35392 Giessen, Germany.
authors: Axel
authors: A
authors: Weber
authors: Institute of Physiological Chemistry, Medical School Hannover, 30625 Hannover, Germany.
authors: Oliver
authors: O
authors: Dittrich-Breiholz
authors: Institute of Physiological Chemistry, Medical School Hannover, 30625 Hannover, Germany.
authors: Heike
authors: H
authors: Schneider
authors: Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
authors: Sabin
authors: S
authors: Bhuju
authors: Institute of Biochemistry, Justus-Liebig-University Giessen, 35392 Giessen, Germany.
authors: Vera V
authors: VV
authors: Saul
authors: Institute of Biochemistry, Justus-Liebig-University Giessen, 35392 Giessen, Germany.
authors: M Lienhard
authors: ML
authors: Schmitz
authors: Rudolf-Buchheim-Institute of Pharmacology, Justus-Liebig-University Giessen, 35392 Giessen, Germany. Electronic address: michael.kracht@pharma.med.uni-giessen.de.
authors: Michael
authors: M
authors: Kracht