Heterochromatin protein 1 gamma and IκB kinase alpha interdependence during tumour necrosis factor gene transcription elongation in activated macrophages.
IκB kinase α (IKKα) is part of the cytoplasmic IKK complex regulating nuclear factor-κB (NF-κB) release and translocation into the nucleus in response to pro-inflammatory signals. IKKα can also be recruited directly to the promoter of NF-κB-dependent genes by NF-κB where it phosphorylates histone H3 at serine 10, triggering recruitment of the bromodomain-containing protein 4 and the positive transcription elongation factor b. Herein, we report that IKKα travels with the elongating form of ribonucleic acid polymerase II together with heterochromatin protein 1 gamma (HP1γ) at NF-κB-dependent genes in activated macrophages. IKKα binds to and phosphorylates HP1γ, which in turn controls IKKα binding to chromatin and phosphorylation of the histone variant H3.3 at serine 31 within transcribing regions. Downstream of transcription end sites, IKKα accumulates with its inhibitor the CUE-domain containing protein 2, suggesting a link between IKKα inactivation and transcription termination.
Section of Experimental Haematology, Leeds Institute of Molecular Medicine, University of Leeds, Wellcome Trust Brenner Building, St. James's University Hospital, Leeds LS9 7TF, UK.
James L
JL
Thorne
Lylia
L
Ouboussad
Pascal F
PF
Lefevre
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D054405:Chemokine CCL3 / Q000235:genetics; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D051550:I-kappa B Kinase / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D012319:RNA Polymerase II / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
C576361:CUEDC2 protein, mouse; C453799:Cbx3 protein, mouse; C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D008070:Lipopolysaccharides; D012097:Repressor Proteins; D014409:Tumor Necrosis Factor-alpha; D051550:I-kappa B Kinase; D012319:RNA Polymerase II