ERRα induces H3K9 demethylation by LSD1 to promote cell invasion.
Fiche publication
Date publication
avril 2017
Journal
Proceedings of the National Academy of Sciences of the United States of America
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BILLAS Isabelle
Tous les auteurs :
Carnesecchi J, Forcet C, Zhang L, Tribollet V, Barenton B, Boudra R, Cerutti C, Billas IM, Sérandour AA, Carroll JS, Beaudoin C, Vanacker JM
Lien Pubmed
Résumé
Lysine Specific Demethylase 1 (LSD1) removes mono- and dimethyl groups from lysine 4 of histone H3 (H3K4) or H3K9, resulting in repressive or activating (respectively) transcriptional histone marks. The mechanisms that control the balance between these two antagonist activities are not understood. We here show that LSD1 and the orphan nuclear receptor estrogen-related receptor α (ERRα) display commonly activated genes. Transcriptional activation by LSD1 and ERRα involves H3K9 demethylation at the transcriptional start site (TSS). Strikingly, ERRα is sufficient to induce LSD1 to demethylate H3K9 in vitro. The relevance of this mechanism is highlighted by functional data. LSD1 and ERRα coregulate several target genes involved in cell migration, including the MMP1 matrix metallo-protease, also activated through H3K9 demethylation at the TSS. Depletion of LSD1 or ERRα reduces the cellular capacity to invade the extracellular matrix, a phenomenon that is rescued by MMP1 reexpression. Altogether our results identify a regulatory network involving a direct switch in the biochemical activities of a histone demethylase, leading to increased cell invasion.
Mots clés
ERRα, LSD1, cell migration, histone demethylation, transcriptional regulation
Référence
Proc Natl Acad Sci U S A. 2017 04 11;114(15):3909-3914