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Title: Identification of a genomic enhancer that enforces proper apoptosis induction in thymic negative selection
Authors: Arai Hojo, Miki
Masuda, Kyoko
Hojo, Hiroaki
Nagahata, Yosuke
Yasuda, Keiko  kyouindb  KAKEN_id
Ohara, Daiya
Takeuchi, Yusuke
Hirota, Keiji  kyouindb  KAKEN_id  orcid (unconfirmed)
Suzuki, Yutaka
Kawamoto, Hiroshi  kyouindb  KAKEN_id  orcid (unconfirmed)
Kawaoka, Shinpei  kyouindb  KAKEN_id
Author's alias: 増田, 喬子
長畑, 洋佑
河本, 宏
河岡, 慎平
Issue Date: 13-Jun-2019
Publisher: Springer Science and Business Media LLC
Journal title: Nature communications
Volume: 10
Thesis number: 2603
Abstract: During thymic negative selection, autoreactive thymocytes carrying T cell receptor (TCR) with overtly strong affinity to self-MHC/self-peptide are removed by Bim-dependent apoptosis, but how Bim is specifically regulated to link TCR activation and apoptosis induction is unclear. Here we identify a murine T cell-specific genomic enhancer EBAB (Bub1-Acoxl-Bim), whose deletion leads to accumulation of thymocytes expressing high affinity TCRs. Consistently, EBAB knockout mice have defective negative selection and fail to delete autoreactive thymocytes in various settings, with this defect accompanied by reduced Bim expression and apoptosis induction. By contrast, EBAB is dispensable for maintaining peripheral T cell homeostasis via Bim-dependent pathways. Our data thus implicate EBAB as an important, developmental stage-specific regulator of Bim expression and apoptosis induction to enforce thymic negative selection and suppress autoimmunity. Our study unravels a part of genomic enhancer codes that underlie complex and context-dependent gene regulation in TCR signaling.
Rights: © The Author(s) 2019 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
DOI(Published Version): 10.1038/s41467-019-10525-1
PubMed ID: 31197149
Appears in Collections:Journal Articles

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