| First Author | Tartey S | Year | 2014 |
| Journal | EMBO J | Volume | 33 |
| Issue | 20 | Pages | 2332-48 |
| PubMed ID | 25107474 | Mgi Jnum | J:216064 |
| Mgi Id | MGI:5607662 | Doi | 10.15252/embj.201488447 |
| Citation | Tartey S, et al. (2014) Akirin2 is critical for inducing inflammatory genes by bridging IkappaB-zeta and the SWI/SNF complex. EMBO J 33(20):2332-48 |
| abstractText | Transcription of inflammatory genes in innate immune cells is coordinately regulated by transcription factors, including NF-kappaB, and chromatin modifiers. However, it remains unclear how microbial sensing initiates chromatin remodeling. Here, we show that Akirin2, an evolutionarily conserved nuclear protein, bridges NF-kappaB and the chromatin remodeling SWI/SNF complex by interacting with BRG1-Associated Factor 60 (BAF60) proteins as well as IkappaB-zeta, which forms a complex with the NF-kappaB p50 subunit. These interactions are essential for Toll-like receptor-, RIG-I-, and Listeria-mediated expression of proinflammatory genes including Il6 and Il12b in macrophages. Consistently, effective clearance of Listeria infection required Akirin2. Furthermore, Akirin2 and IkappaB-zeta recruitment to the Il6 promoter depend upon the presence of IkappaB-zeta and Akirin2, respectively, for regulation of chromatin remodeling. BAF60 proteins were also essential for the induction of Il6 in response to LPS stimulation. Collectively, the IkappaB-zeta-Akirin2-BAF60 complex physically links the NF-kappaB and SWI/SNF complexes in innate immune cell activation. By recruiting SWI/SNF chromatin remodellers to IkappaB-zeta, transcriptional coactivator for NF-kappaB, the conserved nuclear protein Akirin2 stimulates pro-inflammatory gene promoters in mouse macrophages during innate immune responses to viral or bacterial infection. |
