Heterochromatin protein 1 gamma and IκB kinase alpha interdependence during tumour necrosis factor gene transcription elongation in activated macrophages

• Published in: Nucleic acids research Vol. 40; no. 16; pp. 7676 - 7689
• Main Authors: Thorne, James L., Ouboussad, Lylia, Lefevre, Pascal F.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.09.2012
• Subjects: Animals; Cell Line; Cells, Cultured; Chemokine CCL3 - genetics; Chromatin; Chromatin - metabolism; Chromosomal Proteins, Non-Histone - metabolism; Gene Regulation, Chromatin and Epigenetics; Heterochromatin protein 1; Histone H3; Histones; Histones - metabolism; I Kappa B kinase; I-kappa B Kinase - metabolism; IKK protein; Inflammation; Lipopolysaccharides - pharmacology; Macrophage Activation; Macrophages; Macrophages - drug effects; Macrophages - metabolism; Mice; NF- Kappa B protein; Nuclear transport; Phosphorylation; Promoters; Recruitment; Repressor Proteins - metabolism; RNA Polymerase II - metabolism; Serine; Transcription elongation; transcription elongation factor b; Transcription termination; Transcription, Genetic; Travel; Tumor necrosis factor; Tumor Necrosis Factor-alpha - genetics
• ISSN: 0305-1048; 1362-4962; 1362-4962
• DOI: 10.1093/nar/gks509

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.