Role of PBAF and Mediator kinase module in the RELA-dependent activation of CXCL1–3 inflammation genes of the NF-kB pathway

Our results demonstrate that the PBAF complex and the Mediator kinase module regulate distinct, sequential steps in the transcription cycle of CXCL1-3 genes. PBAF is critical for the initial promoter recruitment or stabilization of the transcription machinery, while MKM primarily facilitates the transition into productive elongation. Their additive positive effect and physical interaction suggest a coordinated mechanism where PBAF establishes a permissive chromatin context, enabling subsequent MKM-dependent phosphorylation events that drive the transcriptional burst of key inflammatory chemokines.