Direct access Research units

Epigenetic control study of the inflammatory response

Akirin activates, in cooperation with the SWI / SNF complex, a subset of NF-kB Relish factor target genes, characterized by the presence of H3K4ac markings on their promoters

Downstream of NF-kB signaling pathways activated by inflammatory stimuli, NF-kB transcription factors play a central role. They are responsible for activating hundreds of genes with pro- or anti-inflammatory activity. Using Drosophila as a study model, our team recently isolated a novel member of the IMD pathway called Akirin. This protein, which is conserved among metazoans, is required for NF-kB signaling. Its action is completely original since our work has shown that Akirin acts as a selector capable of influencing the choice of target genes for NF-kB to be transcribed, in insects as well as in mammals. Akirins allow the NF-kB factor to preferentially target genes with activity

pro-inflammatory and not the genes involved in resolving inflammation. This type of selective molecule therefore represents the “missing link” for understanding the selectivity of NF-kB signaling.

Our work shows that Akirin acts in the regulation of NF-kB signaling pathways via the recruitment of the SWI / SNF chromatin remodeling complex, and the deposition of specific epigenetic marks on the promoters of the target genes of NF-kB and dependent on Akirin.

We propose to identify in Drosophila and human and murine cell lines, the epigenetic mechanisms involved in the control of the transcriptional selectivity of the target genes of NF-kB.