Fiche publication
Date publication
novembre 2015
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DAVIDSON Irwin
Tous les auteurs :
Ferri F, Parcelier A, Petit V, Gallouet AS, Lewandowski D, Dalloz M, van den Heuvel A, Kolovos P, Soler E, Squadrito ML, De Palma M, Davidson I, Rousselet G, Romeo PH
Lien Pubmed
Résumé
Despite its importance during viral or bacterial infections, transcriptional regulation of the interferon-β gene (Ifnb1) in activated macrophages is only partially understood. Here we report that TRIM33 deficiency results in high, sustained expression of Ifnb1 at late stages of toll-like receptor-mediated activation in macrophages but not in fibroblasts. In macrophages, TRIM33 is recruited by PU.1 to a conserved region, the Ifnb1 Control Element (ICE), located 15 kb upstream of the Ifnb1 transcription start site. ICE constitutively interacts with Ifnb1 through a TRIM33-independent chromatin loop. At late phases of lipopolysaccharide activation of macrophages, TRIM33 is bound to ICE, regulates Ifnb1 enhanceosome loading, controls Ifnb1 chromatin structure and represses Ifnb1 gene transcription by preventing recruitment of CBP/p300. These results characterize a previously unknown mechanism of macrophage-specific regulation of Ifnb1 transcription whereby TRIM33 is critical for Ifnb1 gene transcription shutdown.
Mots clés
Animals, Female, Gene Expression Regulation, Interferon-beta, genetics, Macrophage Activation, Macrophages, cytology, Male, Mice, Mice, Inbred C57BL, Transcription Factors, genetics, Transcription, Genetic
Référence
Nat Commun. 2015 Nov;6:8900
