@article{0db2013cf3854bd38ef94fa6b4eef505,
title = "The acetyltransferase KAT7 is required for thymic epithelial cell expansion, expression of AIRE target genes, and thymic tolerance",
abstract = "The autoimmune regulator (AIRE) induces the transcription of thousands of peripheral tissue genes (PTGs) in thymic epithelial cells (TECs) to mediate immunological tolerance. The chromatin state required for optimal AIRE function in TECs and how this state is induced remains unclear. We tested the role of the histone acetyltransferase, KAT7 (also known as HBO1 or MYST2), which is essential for acetylation of histone 3 lysine 14, in TEC differentiation, AIRE-mediated PTG expression, and thymic tolerance. We find that KAT7 is required for optimal expansion of medullary TEC and has a major role in the expression of AIRE-dependent PTGs, associated with enhanced chromatin accessibility at these gene loci in TECs. Mice with TEC-specific deletion develop organ-specific autoimmunity with features resembling those observed in -deficient mice. These findings highlight critical roles for KAT7-mediated acetylation in promoting a chromatin state at PTG loci that enables AIRE function and the establishment of immunological tolerance.",
author = "Melanie Heinlein and Gandolfo, \{Luke C\} and Kelin Zhao and Teh, \{Charis E\} and Nghi Nguyen and Baell, \{Jonathan B\} and Yael Goldfarb and Jakub Abramson and Johannes Wichmann and Voss, \{Anne K\} and Andreas Strasser and Smyth, \{Gordon K\} and Tim Thomas and Gray, \{Daniel H D\}",
note = "We thank G. Hollander for the Foxn1Cre mice; D. Mathis for Aire-/- mice; the WEHI Flow Cytometry Laboratory and the Centre for Dynamic Imaging for technical help; B. Helbert, K. Mackwell, and C. Young for mouse genotyping; G. Siciliano, H. Marks, K. Humphreys, and S. O{\textquoteright}Connor for animal husbandry; S. Wilcox, N. Bediaga, G. Naselli, and B. Pal for technical advice and assistance with ATAC-seq. Funding: This work was supported by the National Health and Medical Research Council Australia Grants or Fellowships (1089072 to C.E.T.; 1020363 and 1016701 to A.S.; 1078763, 1121325, 1090236, 1158024, and 1187367 to D.H.D.G.; 575558, 1003435, 1081421, and 1084248 to A.K.V. and T.T.; 1080146 to T.T. and J.B.B.; 1020411 and 1117602 to J.B.B.; and 1154970 to G.K.S.) and Australian Government Research Training Program Scholarship and Boehringer Ingelheim Fonds travel grant (to M.H.). Research in the Abramson laboratory is supported by the European Research Council (ERC-2016-CoG-724821), Israel Science Foundation (1919/21), and the Bill and Marika Glied and Family Fund. The Thomas and Voss laboratories receive research funding from Cancer Therapeutics Cooperative Research Centre. The Australian Translational Medicinal Chemistry Facility (ATMCF) within Monash Institute of Pharmaceutical Sciences (MIPS) acknowledges the support of the Australian Government{\textquoteright}s National Collaborative Research Infrastructure Strategy (NCRIS) program via Therapeutic Innovation Australia (TIA). This research was made possible by a Victorian State Government Operational Infrastructure Support and the Independent Research Institutes Infrastructure Support Scheme of the Australian Government National Health and Medical Research Council.",
year = "2022",
month = jan,
day = "21",
doi = "10.1126/sciimmunol.abb6032",
language = "الإنجليزيّة",
volume = "7",
pages = "eabb6032",
journal = "Science Immunology",
issn = "2470-9468",
publisher = "American Association for the Advancement of Science",
number = "67",
}