The Transcription Factor ATF7 Mediates Lipopolysaccharide-induced Epigenetic Changes in Macrophages Involved in Innate Immunological Memory

Overview

Journal Nat Immunol

Date 2015 Sep 1

PMID 26322480

Citations 100

Authors

Keisuke Yoshida

Toshio Maekawa

Yujuan Zhu

Claire Renard-Guillet

Bruno Chatton

Kentaro Inoue

Takeru Uchiyama

Ken-Ichi Ishibashi

Takuji Yamada

Naohito Ohno

Katsuhiko Shirahige

Mariko Okada-Hatakeyama

Shunsuke Ishii

Affiliations

Soon will be listed here.

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.

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References

Liu C, Schreiber S, Bernstein B . Development and validation of a T7 based linear amplification for genomic DNA. BMC Genomics. 2003; 4(1):19. PMC: 161798. DOI: 10.1186/1471-2164-4-19. View

Kawai T, Akira S . The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010; 11(5):373-84. DOI: 10.1038/ni.1863. View

van Essen D, Zhu Y, Saccani S . A feed-forward circuit controlling inducible NF-κB target gene activation by promoter histone demethylation. Mol Cell. 2010; 39(5):750-60. DOI: 10.1016/j.molcel.2010.08.010. View

Durrant W, Dong X . Systemic acquired resistance. Annu Rev Phytopathol. 2004; 42:185-209. DOI: 10.1146/annurev.phyto.42.040803.140421. View

Yona S, Kim K, Wolf Y, Mildner A, Varol D, Breker M . Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity. 2013; 38(1):79-91. PMC: 3908543. DOI: 10.1016/j.immuni.2012.12.001. View

Shivers R, Pagano D, Kooistra T, Richardson C, Reddy K, Whitney J . Phosphorylation of the conserved transcription factor ATF-7 by PMK-1 p38 MAPK regulates innate immunity in Caenorhabditis elegans. PLoS Genet. 2010; 6(4):e1000892. PMC: 2848548. DOI: 10.1371/journal.pgen.1000892. View

Sano Y, Harada J, Tashiro S, Maekawa T, Ishii S . ATF-2 is a common nuclear target of Smad and TAK1 pathways in transforming growth factor-beta signaling. J Biol Chem. 1999; 274(13):8949-57. DOI: 10.1074/jbc.274.13.8949. View

Hai T, Liu F, Coukos W, Green M . Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers. Genes Dev. 1989; 3(12B):2083-90. DOI: 10.1101/gad.3.12b.2083. View

Ghisletti S, Barozzi I, Mietton F, Polletti S, De Santa F, Venturini E . Identification and characterization of enhancers controlling the inflammatory gene expression program in macrophages. Immunity. 2010; 32(3):317-28. DOI: 10.1016/j.immuni.2010.02.008. View

10.

Ahmed R, Bevan M, Reiner S, Fearon D . The precursors of memory: models and controversies. Nat Rev Immunol. 2009; 9(9):662-8. DOI: 10.1038/nri2619. View

11.

Maekawa T, Sakura H, Sudo T, Yoshimura T, Fujisawa J, Yoshida M . Leucine zipper structure of the protein CRE-BP1 binding to the cyclic AMP response element in brain. EMBO J. 1989; 8(7):2023-8. PMC: 401081. DOI: 10.1002/j.1460-2075.1989.tb03610.x. View

12.

Pham L, Dionne M, Shirasu-Hiza M, Schneider D . A specific primed immune response in Drosophila is dependent on phagocytes. PLoS Pathog. 2007; 3(3):e26. PMC: 1817657. DOI: 10.1371/journal.ppat.0030026. View

13.

Ichimura T, Watanabe S, Sakamoto Y, Aoto T, Fujita N, Nakao M . Transcriptional repression and heterochromatin formation by MBD1 and MCAF/AM family proteins. J Biol Chem. 2005; 280(14):13928-35. DOI: 10.1074/jbc.M413654200. View

14.

Hashimoto D, Chow A, Noizat C, Teo P, Beasley M, Leboeuf M . Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity. 2013; 38(4):792-804. PMC: 3853406. DOI: 10.1016/j.immuni.2013.04.004. View

15.

GORHE D . Inhibition of multiplication of foot and mouth disease virus in adult mice pretreated with Freund's complete adjuvant. Nature. 1967; 216(5121):1242-4. DOI: 10.1038/2161242a0. View

16.

Shinkai Y, Tachibana M . H3K9 methyltransferase G9a and the related molecule GLP. Genes Dev. 2011; 25(8):781-8. PMC: 3078703. DOI: 10.1101/gad.2027411. View

17.

Ahmad K, Henikoff S . The histone variant H3.3 marks active chromatin by replication-independent nucleosome assembly. Mol Cell. 2002; 9(6):1191-200. DOI: 10.1016/s1097-2765(02)00542-7. View

18.

Kleinnijenhuis J, Quintin J, Preijers F, Joosten L, Ifrim D, Saeed S . Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc Natl Acad Sci U S A. 2012; 109(43):17537-42. PMC: 3491454. DOI: 10.1073/pnas.1202870109. View

19.

Groom J, Luster A . CXCR3 ligands: redundant, collaborative and antagonistic functions. Immunol Cell Biol. 2011; 89(2):207-15. PMC: 3863330. DOI: 10.1038/icb.2010.158. View

20.

Benn C, Netea M, Selin L, Aaby P . A small jab - a big effect: nonspecific immunomodulation by vaccines. Trends Immunol. 2013; 34(9):431-9. DOI: 10.1016/j.it.2013.04.004. View