title: The regulation of TIM-3 transcription in T cells involves c-Jun binding but not CpG methylation at the TIM-3 promoter.
abstract: Tim-3 is an immunomodulatory protein that is expressed constitutively on monocytes but is induced in activated T cells. The mechanisms involved in the regulation of TIM-3 transcription are poorly understood. In the present study, we investigated whether methylation of the TIM-3 promoter is involved in regulatingTIM-3 transcription in T cells, and identified a transcription factor that regulates TIM-3 transcription by associating with the TIM-3 minimal promoter region. Pyrosequencing of the TIM-3 promoter up to -1440bp revealed 11 hypermethylated CpG sites and 4 hypomethylated CpG sites in human CD4(+) T cells as well as in CD11b(+) cells. Dimethylation of histone H3 lysine 4 (H3K4), a mark of transcriptional activation, was predominantly found in the proximal TIM-3 promoter -954 to -34bp region, whereas trimethylation of H3K9 and H3K27, which are markers of transcriptional suppression, were mostly observed in the distal promoter -1549 to -1048bp region in human CD4(+) T cells and CD11b(+) cells. However, no change in the methylation status of CpG sites and the histone H3 in the TIM-3 promoter was found during induction of TIM-3 transcription in T cells. Finally, AP-1 involvement in TIM-3 transcription was shown in relation with the TIM-3 minimal promoter -146 to +144bp region. The present study defines the minimal TIM-3 promoter region and demonstrates its interaction with c-Jun during TIM-3 transcription in CD4(+) T cells.
authors.affiliation: Department of Microbiology, Ajou University School of Medicine, Ajou University, Youngtongku Wonchondong San 5, Suwon 442-749, Republic of Korea; Department of Biomedical Sciences, The Graduate School, Ajou University, Youngtongku Wonchondong San 5, Suwon 442-749, Republic of Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Yun
authors.affiliation: Department of Microbiology, Ajou University School of Medicine, Ajou University, Youngtongku Wonchondong San 5, Suwon 442-749, Republic of Korea; Department of Biomedical Sciences, The Graduate School, Ajou University, Youngtongku Wonchondong San 5, Suwon 442-749, Republic of Korea.
authors.forename: Ka-Jung
authors.initials: KJ
authors.lastname: Jun
authors.affiliation: Department of Microbiology, Ajou University School of Medicine, Ajou University, Youngtongku Wonchondong San 5, Suwon 442-749, Republic of Korea; Department of Biomedical Sciences, The Graduate School, Ajou University, Youngtongku Wonchondong San 5, Suwon 442-749, Republic of Korea.
authors.forename: Kuniharu
authors.initials: K
authors.lastname: Komori
authors.affiliation: Department of Microbiology, Ajou University School of Medicine, Ajou University, Youngtongku Wonchondong San 5, Suwon 442-749, Republic of Korea.
authors.forename: Mi Jin
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Ajou University School of Medicine, Ajou University, Youngtongku Wonchondong San 5, Suwon 442-749, Republic of Korea; Department of Biomedical Sciences, The Graduate School, Ajou University, Youngtongku Wonchondong San 5, Suwon 442-749, Republic of Korea.
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Kwon
authors.affiliation: Department of Microbiology, Ajou University School of Medicine, Ajou University, Youngtongku Wonchondong San 5, Suwon 442-749, Republic of Korea; Department of Biomedical Sciences, The Graduate School, Ajou University, Youngtongku Wonchondong San 5, Suwon 442-749, Republic of Korea.
authors.forename: Yong-Joon
authors.initials: YJ
authors.lastname: Chwae
authors.affiliation: Department of Microbiology, Ajou University School of Medicine, Ajou University, Youngtongku Wonchondong San 5, Suwon 442-749, Republic of Korea; Department of Biomedical Sciences, The Graduate School, Ajou University, Youngtongku Wonchondong San 5, Suwon 442-749, Republic of Korea.
authors.forename: Kyongmin
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Ajou University School of Medicine, Ajou University, Youngtongku Wonchondong San 5, Suwon 442-749, Republic of Korea; Department of Biomedical Sciences, The Graduate School, Ajou University, Youngtongku Wonchondong San 5, Suwon 442-749, Republic of Korea.
authors.forename: Ho-Joon
authors.initials: HJ
authors.lastname: Shin
authors.affiliation: Department of Microbiology, Ajou University School of Medicine, Ajou University, Youngtongku Wonchondong San 5, Suwon 442-749, Republic of Korea; Department of Biomedical Sciences, The Graduate School, Ajou University, Youngtongku Wonchondong San 5, Suwon 442-749, Republic of Korea. Electronic address: sinsun@ajou.ac.kr.
authors.forename: Sun
authors.initials: S
authors.lastname: Park
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D047369:Chromatin Immunoprecipitation; D018899:CpG Islands / Q000235:genetics / Q000276:immunology; D019175:DNA Methylation / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D000072597:Hepatitis A Virus Cellular Receptor 2 / Q000096:biosynthesis*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000276:immunology; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000276:immunology / Q000378:metabolism
chemical_list: C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D006657:Histones; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1
keywords: AP-1; CD4(+) T cells; DNA methylation; Histone methylation; Tim-3; Transcription