Heterochromatin protein 1 gamma and I?B kinase alpha interdependence during tumour necrosis factor gene transcription elongation in activated macrophages.

ABSTRACT: I?B kinase ? (IKK?) is part of the cytoplasmic IKK complex regulating nuclear factor-?B (NF-?B) release and translocation into the nucleus in response to pro-inflammatory signals. IKK? can also be recruited directly to the promoter of NF-?B-dependent genes by NF-?B 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 IKK? travels with the elongating form of ribonucleic acid polymerase II together with heterochromatin protein 1 gamma (HP1?) at NF-?B-dependent genes in activated macrophages. IKK? binds to and phosphorylates HP1?, which in turn controls IKK? binding to chromatin and phosphorylation of the histone variant H3.3 at serine 31 within transcribing regions. Downstream of transcription end sites, IKK? accumulates with its inhibitor the CUE-domain containing protein 2, suggesting a link between IKK? inactivation and transcription termination.

SUBMITTER: Thorne JL 

PROVIDER: S-EPMC3439902 | biostudies-other | 2012 Sep

REPOSITORIES: biostudies-other