GSE107989
PKCa-LSD1-NF-?B Signaling Cascade Is Crucial for Epigenetic Control of the Inflammatory Response [ChIP-Seq]
The inflammatory response mediated by NF-?B signaling is essential for host defense against pathogens. Although the components and regulatory mechanism of NF-?B signaling have been well-studied, molecular basis for the epigenetic regulation of the inflammatory response is poorly understood. Here, we identify a new signaling axis of PKCa- LSD1-NF-?B p65 which is critical for activation and amplification of the inflammatory response and triggering systemic inflammatory diseases. In response to excessive inflammatory stimuli, PKCa translocates to the nucleus and phosphorylates LSD1. Phosphorylation of LSD1 is required for its interaction with p65 and facilitates demethylation of p65 leading to enhanced protein stability. Genome-wide analysis reveals a critical role of LPS-induced LSD1 phosphorylation in the transcriptional activation of NF-?B target genes. Together, we demonstrate that PKCa-LSD1-NF-?B signaling cascade is crucial for epigenetic control of the inflammatory response. Overall design: Examination of LSD1 and p65 in WT BMDMs upon LPS