title: The transcription factor ATF7 mediates lipopolysaccharide-induced epigenetic changes in macrophages involved in innate immunological memory.
abstract: Immunological memory is thought to be mediated exclusively by lymphocytes. However, enhanced innate immune responses caused by a previous infection increase protection against reinfection, which suggests the presence of innate immunological memory. Here we identified an important role for the stress-response transcription factor ATF7 in innate immunological memory. ATF7 suppressed a group of genes encoding factors involved in innate immunity in macrophages by recruiting the histone H3K9 dimethyltransferase G9a. Treatment with lipopolysaccharide, which mimics bacterial infection, induced phosphorylation of ATF7 via the kinase p38, which led to the release of ATF7 from chromatin and a decrease in repressive histone H3K9me2 marks. A partially disrupted chromatin structure and increased basal expression of target genes were maintained for long periods, which enhanced resistance to pathogens. ATF7 might therefore be important in controlling memory in cells of the innate immune system.
authors: Laboratory of Molecular Genetics, CREST Research Project of the Japan Science and Technology Agency, RIKEN Tsukuba Institute, Tsukuba, Japan.
authors: Keisuke
authors: K
authors: Yoshida
authors: Laboratory of Molecular Genetics, CREST Research Project of the Japan Science and Technology Agency, RIKEN Tsukuba Institute, Tsukuba, Japan.
authors: Toshio
authors: T
authors: Maekawa
authors: Laboratory of Molecular Genetics, CREST Research Project of the Japan Science and Technology Agency, RIKEN Tsukuba Institute, Tsukuba, Japan.|Department of Functional Genomics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
authors: Yujuan
authors: Y
authors: Zhu
authors: Laboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.
authors: Claire
authors: C
authors: Renard-Guillet
authors: Université de Strasbourg, UMR7242 Biotechnologie et Signalisation Cellulaire, Illkirch, France.
authors: Bruno
authors: B
authors: Chatton
authors: Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors: Kentaro
authors: K
authors: Inoue
authors: Department of Biological Information, Tokyo Institute of Technology, Graduate School of Bioscience and Biotechnology, Yokohama, Japan.
authors: Takeru
authors: T
authors: Uchiyama
authors: Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy &Life Sciences, Tokyo, Japan.
authors: Ken-ichi
authors: K
authors: Ishibashi
authors: Department of Biological Information, Tokyo Institute of Technology, Graduate School of Bioscience and Biotechnology, Yokohama, Japan.
authors: Takuji
authors: T
authors: Yamada
authors: Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy &Life Sciences, Tokyo, Japan.
authors: Naohito
authors: N
authors: Ohno
authors: Laboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.
authors: Katsuhiko
authors: K
authors: Shirahige
authors: Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors: Mariko
authors: M
authors: Okada-Hatakeyama
authors: Laboratory of Molecular Genetics, CREST Research Project of the Japan Science and Technology Agency, RIKEN Tsukuba Institute, Tsukuba, Japan.|Department of Functional Genomics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
authors: Shunsuke
authors: S
authors: Ishii
mesh_terms: D051696:Activating Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000276:immunology*; D007156:Immunologic Memory / Q000235:genetics* / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C427752:ATF7 protein, human; D051696:Activating Transcription Factors; D008070:Lipopolysaccharides