C/EBPδ-induced epigenetic changes control the dynamic gene transcription of S100a8 and S100a9.

ABSTRACT: The proinflammatory alarmins S100A8 and S100A9 are among the most abundant proteins in neutrophils and monocytes but are completely silenced after differentiation to macrophages. The molecular mechanisms of the extraordinarily dynamic transcriptional regulation of S100a8 and S100a9 genes, however, are only barely understood. Using an unbiased genome-wide CRISPR/Cas9 knockout (KO)-based screening approach in immortalized murine monocytes, we identified the transcription factor C/EBPδ as a central regulator of S100a8 and S100a9 expression. We showed that S100A8/A9 expression and thereby neutrophil recruitment and cytokine release were decreased in C/EBPδ KO mice in a mouse model of acute lung inflammation. S100a8 and S100a9 expression was further con

SUBMITTER: Jauch-Speer SL 

PROVIDER: S-EPMC9122501 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature