Proposed model of LPS-induced CD40 gene expression. LPS activates NF-κB, which leads to subsequent nuclear translocation and binding of p65 and p50 to NF-κB elements in the CD40 promoter. Concurrently, LPS induces IRF-3 expression, which activates IFN-β expression. This leads to the subsequent activation of STAT-1α, which then dimerizes, translocates into the nucleus, and binds to GAS elements in the CD40 promoter with delayed kinetics compared with NF-κB p65 and p50. Concurrent with NF-κB and STAT-1α recruitment, LPS leads to modifications in H3 and H4 and to recruitment of RNA Pol II. The sequential recruitment of transcription factors and Pol II to the CD40 promoter, in conjunction with permissive histone modifications, results in transcriptional activation of the CD40 gene. See “Discussion” for details. MD2 indicates the cofactor for TLR4; TIRAP, Toll-IL-1R domain-containing adapter protein; TYK2, tyrosine kinase-2.