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Nat Immunol. 2015 Oct;16(10):1034-43. doi: 10.1038/ni.3257. Epub 2015 Aug 31.

The transcription factor ATF7 mediates lipopolysaccharide-induced epigenetic changes in macrophages involved in innate immunological memory.

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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.
Laboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.
Université de Strasbourg, UMR7242 Biotechnologie et Signalisation Cellulaire, Illkirch, France.
Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Department of Biological Information, Tokyo Institute of Technology, Graduate School of Bioscience and Biotechnology, Yokohama, Japan.
Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy &Life Sciences, Tokyo, Japan.


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.

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