Infection Reveals a Modification of SIRT2 Critical for Chromatin Association
Jorge M. Pereira,
Christine Chevalier,
Thibault Chaze,
Quentin Gianetto,
Francis Impens,
Mariette Matondo,
Pascale Cossart,
Mélanie A. Hamon
Affiliations
Jorge M. Pereira
Institut Pasteur, Unité des Interactions Bactéries-Cellules, Paris, France; Institut National de la Santé et de la Recherche Médicale, U604, Paris, France; Institut National de la Recherche Agronomique, USC2020, Paris, France; Institut Pasteur, Chromatine et Infection G5, Paris, France
Christine Chevalier
Institut Pasteur, Chromatine et Infection G5, Paris, France
Thibault Chaze
Institut Pasteur, Unité de Spectrométrie de Masse Structurale et Protéomique, Paris, France
Quentin Gianetto
Institut Pasteur, Unité de Spectrométrie de Masse Structurale et Protéomique, Paris, France
Francis Impens
Institut Pasteur, Unité des Interactions Bactéries-Cellules, Paris, France; Institut National de la Santé et de la Recherche Médicale, U604, Paris, France; Institut National de la Recherche Agronomique, USC2020, Paris, France; Center for Medical Biotechnology, VIB, Ghent University, 9000 Ghent, Belgium
Mariette Matondo
Institut Pasteur, Unité de Spectrométrie de Masse Structurale et Protéomique, Paris, France
Pascale Cossart
Institut Pasteur, Unité des Interactions Bactéries-Cellules, Paris, France; Institut National de la Santé et de la Recherche Médicale, U604, Paris, France; Institut National de la Recherche Agronomique, USC2020, Paris, France; Corresponding author
Mélanie A. Hamon
Institut Pasteur, Chromatine et Infection G5, Paris, France; Corresponding author
Summary: Sirtuin 2 is a nicotinamide-adenine-dinucleotide-dependent deacetylase that regulates cell processes such as carcinogenesis, cell cycle, DNA damage, and infection. Subcellular localization of SIRT2 is crucial for its function but is poorly understood. Infection with the bacterial pathogen Listeria monocytogenes, which relocalizes SIRT2 from the cytoplasm to the chromatin, provides an ideal stimulus for the molecular study of this process. In this report, we provide a map of SIRT2 post-translational modification sites and focus on serine 25 phosphorylation. We show that infection specifically induces dephosphorylation of S25, an event essential for SIRT2 chromatin association. Furthermore, we identify a nuclear complex formed by the phosphatases PPM1A and PPM1B, with SIRT2 essential for controlling H3K18 deacetylation and SIRT2-mediated gene repression during infection and necessary for a productive Listeria infection. This study reveals a molecular mechanism regulating SIRT2 function and localization, paving the way for understanding other SIRT2-regulated cellular processes. : Sirtuins are enzymes critical for various processes, including genomic stability, metabolism, and aging. Through study of Listeria monocytogenes, a bacterial pathogen that exploits SIRT2 for productive infection, Pereira et al. uncover a SIRT2 modification necessary for chromatin association and function. Keywords: chromatin, sirtuin, Listeria monocytogenes, phosphorylation, PPM1, histone acetylation, H3K18, infection, subcellular localization
