C-terminal binding protein 2 in macrophage inflammation [RNA-seq]

Acute inflammation is critical for survival, but chronic immune mediated inflammation is a leading cause for disease and mortality worldwide , while our understanding of the pathogenesis and precise treatments are still limited. Here we investigate the role of the transcriptional corepressors CTBP 1 and 2 in murine and human macrophage inflammation using loss of function models to show that CTBP2 but not CTBP1 controls inflammatory gene expression . We find that CTBP2 binds to cis-regulatory elements of inflammatory genes together with the transcription factors NFκB and AP-1 and forms a corepressor complex. Rescue of Ctbp1/2 double knockout cells with full length CTBP2 potently represses inflammatory responses while a monomeric mutant does not. Differential profiling of CTBP2’s wild type and monomeric interactome confirms oligomer-specific interactions with multiple repressors including the NuRD complex, WIZ and KDM1A. Conversely, monomers retain their ability to interact with inflammatory transcription factors and polymerase 2, boosting transcription of inflammatory genes. Our findings point to an important function for CTBP2 in the resolution of inflammation, which may contribute to the progression of inflammatory disorders and which may offer therapeutic targets in the future.