Recruitment of RelB to the Csf2 promoter enhances RelA-mediated transcription of granulocyte-macrophage colony-stimulating factor.
Tumor necrosis factor (TNF) induces expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) but lymphotoxin β (LTβ) does not. Here we report that priming of cells with agonistic LTβ receptor antibody synergistically enhanced TNF-induced GM-CSF expression. The LTβ priming process was not due to an increase in TNF-mediated nuclear translocation of p65, p65 DNA binding, or NF-κB transactivational activity. The synergistic effect of LTβ priming was not observed with other TNF-responsive genes such as Ccl2 or RelB, which suggested that this effect was not a general increase in TNF signaling. Furthermore, RelB and p65 were both independently recruited to the GM-CSF promoter when cells were primed with LTβ followed by TNF treatment. As a consequence, an increase in both chromatin accessibility and the recruitment of RNA polymerase II were observed to the GM-CSF promoter. Taken together, these findings suggested that LTβ signaling amplified TNF-mediated GM-CSF expression by facilitating chromatin access and the co-recruitment of RNA polymerase II to increase gene transcription. Moreover, the novel priming process described here underscores the complexity of the interactions between the classical and alternative NF-κB signaling pathways.
Laboratory of Immunology, NIA, National Institutes of Health, Baltimore, Maryland 21224, USA.
Carl Y
CY
Sasaki
Paritosh
P
Ghosh
Dan L
DL
Longo
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D053259:Lymphotoxin beta Receptor / Q000276:immunology / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051996:Transcription Factor RelA / Q000378:metabolism*; D051841:Transcription Factor RelB / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097782:NF-kappaB-Inducing Kinase
D000911:Antibodies, Monoclonal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D053259:Lymphotoxin beta Receptor; D017346:Protein Serine-Threonine Kinases; D012319:RNA Polymerase II; D051996:Transcription Factor RelA; D051841:Transcription Factor RelB; D014409:Tumor Necrosis Factor-alpha; D000097782:NF-kappaB-Inducing Kinase; C505699:Ltbr protein, mouse; C498144:Rela protein, mouse; C497594:Relb protein, mouse