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

IiB kinase a (IKKa) is part of the cytoplasmic IKK complex regulating nuclear factor-{kappa}B (NF-iB) release and translocation into the nucleus in response to pro-inflammatory signals. IKKa can also be recruited directly to the promoter of NF-iB-dependent genes by NF-iB 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 IKKa travels with the elongating form of ribonucleic acid polymerase II together with heterochromatin protein 1 gamma (HP1c) at NF-iBdependent genes in activated macrophages. IKKa binds to and phosphorylates HP1c, which in turn controls IKKa binding to chromatin and phosphorylation of the histone variant H3.3 at serine 31 within transcribing regions. Downstream of transcription end sites, IKKa accumulates with its inhibitor the CUE-domain containing protein 2, suggesting a link between IKKa inactivation and transcription termination.