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

First Author  Thorne JL Year  2012
Journal  Nucleic Acids Res Volume  40
Issue  16 Pages  7676-89
PubMed ID  22649058 Mgi Jnum  J:198894
Mgi Id  MGI:5499708 Doi  10.1093/nar/gks509
Citation  Thorne JL, et al. (2012) Heterochromatin protein 1 gamma and IkappaB kinase alpha interdependence during tumour necrosis factor gene transcription elongation in activated macrophages. Nucleic Acids Res 40(16):7676-89
abstractText  IkappaB kinase alpha (IKKalpha) is part of the cytoplasmic IKK complex regulating nuclear factor-kappaB (NF-kappaB) release and translocation into the nucleus in response to pro-inflammatory signals. IKKalpha can also be recruited directly to the promoter of NF-kappaB-dependent genes by NF-kappaB 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 IKKalpha travels with the elongating form of ribonucleic acid polymerase II together with heterochromatin protein 1 gamma (HP1gamma) at NF-kappaB-dependent genes in activated macrophages. IKKalpha binds to and phosphorylates HP1gamma, which in turn controls IKKalpha binding to chromatin and phosphorylation of the histone variant H3.3 at serine 31 within transcribing regions. Downstream of transcription end sites, IKKalpha accumulates with its inhibitor the CUE-domain containing protein 2, suggesting a link between IKKalpha inactivation and transcription termination.
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