IL-1β-specific recruitment of GCN5 histone acetyltransferase induces the release of PAF1 from chromatin for the de-repression of inflammatory response genes.
SCIE
SCOPUS
- Title
- IL-1β-specific recruitment of GCN5 histone acetyltransferase induces the release of PAF1 from chromatin for the de-repression of inflammatory response genes.
- Authors
- Nari Kim; Hwa Young Sun; Min Young Youn; Yoo, JY
- Date Issued
- 2013-04
- Publisher
- London, Information Retrieval ltd.
- Abstract
- To determine the functional specificity of inflammation, it is critical to orchestrate the timely activation and repression of inflammatory responses. Here, we explored the PAF1 (RNA polymerase II associated factor)-mediated signal- and locus-specific repression of genes induced through the pro-inflammatory cytokine interleukin (IL)-1 beta. Using microarray analysis, we identified the PAF1 target genes whose expression was further enhanced by PAF1 knockdown in IL-1 beta-stimulated HepG2 hepatocarcinomas. PAF1 bound near the transcription start sites of target genes and dissociated on stimulation. In PAF1-deficient cells, more elongating RNA polymerase II and acetylated histones were observed, although IL-1 beta-mediated activation and recruitment of nuclear factor kappa B (NF-kappa B) were not altered. Under basal conditions, PAF1 blocked histone acetyltransferase general control non-depressible 5 (GCN5)-mediated acetylation on H3K9 and H4K5 residues. On IL-1 beta stimulation, activated GCN5 discharged PAF1 from chromatin, allowing productive transcription to occur. PAF1 bound to histones but not to acetylated histones, and the chromatin-binding domain of PAF1 was essential for target gene repression. Moreover, IL-1 beta-induced cell migration was similarly controlled through counteraction between PAF1 and GCN5. These results suggest that the IL-1 beta signal-specific exchange of PAF1 and GCN5 on the target locus limits inappropriate gene induction and facilitates the timely activation of inflammatory responses.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/11850
- DOI
- 10.1093/NAR/GKT156
- ISSN
- 0305-1048
- Article Type
- Article
- Citation
- NUCLEIC ACIDS RESEARCH, vol. 41, no. 8, page. 4495 - 4506, 2013-04
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