Nonconventional initiation complex assembly by STAT and NF-kappaB transcription factors regulates nitric oxide synthase expression.
Bottom Line: NF-kappaB preceded ISGF3 at the Nos2 promoter and generated a transcriptional memory effect by depositing basal transcription factor TFIIH with the associated CDK7 kinase for serine 5 phosphorylation of the RNA polymerase II (pol II) carboxyterminal domain (CTD).Subsequent to TFIIH deposition by NF-kappaB, ISGF3 attracted the pol II enzyme and phosphorylation at CTD S5 occurred.Thus, STATs and NF-kappaB cooperate through pol II promoter recruitment and the phosphorylation of its CTD, respectively, as a prerequisite for productive elongation of iNOS mRNA.
Affiliation: Max F. Perutz Laboratories, Department of Genetics, Microbiology and Immunobiology, University of Vienna, Dr. Bohr-Gasse 9/4, A1030 Vienna, Austria.Show MeSH
Mentions: Combined treatment of macrophages with IFN-I and hkL produced an increase of histone acetylation at both the proximal and distal promoter locations (Figure 4A). Treatment with IFN-I alone led to an increase of H4 acetylation almost exclusively at the distal IFN response region (Figure 4B). Conversely, hkL treatment alone caused an increase in H4 acetylation predominantly at the proximal NF-κB element (Figure 4C). Our findings suggest that ISGF3 and NF-κB indeed cooperate in producing hyperacetylated Nos2 promoter chromatin, but that their histone acetyl transferase (HAT)-recruiting activities show no signs of functional interdependence.
Affiliation: Max F. Perutz Laboratories, Department of Genetics, Microbiology and Immunobiology, University of Vienna, Dr. Bohr-Gasse 9/4, A1030 Vienna, Austria.