title: Essential role for the histone acetyltransferase KAT7 in T cell development, fitness, and survival.
abstract: Histone acetylation has an important role in gene regulation, DNA replication, and repair. Because these processes are central to the development of the immune system, we investigated the role of a previously unstudied histone acetyltransferase named KAT7 (also known as Myst2 or HBO1) in the regulation of thymopoiesis and observed a critical role in the regulation of conventional and innate-like T cell development. We found that KAT7-deficient thymocytes displayed normal, positive selection and development into mature single-positive αβ thymocytes; however, we observed few peripheral CD4+or CD8+T cells. The observed effects did not appear to arise from alterations to DNA replication, the TCR repertoire, or a block in thymocyte maturation and, more likely, was linked to survival defects related to gene deregulation because KAT7 deficiency led to an almost complete and specific loss of global histone-H3 lysine 14 acetylation (H3K14ac). Overall, we demonstrated a nonredundant role for KAT7 in the maintenance of H3K14ac, which is intimately linked with the ability to develop a normal immune system.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; and.|Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Dane M
authors.initials: DM
authors.lastname: Newman
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; and.|Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Anne K
authors.initials: AK
authors.lastname: Voss
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; and.|Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Tim
authors.initials: T
authors.lastname: Thomas
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; and rallan@wehi.edu.au.|Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Rhys S
authors.initials: RS
authors.lastname: Allan
mesh_terms: D000107:Acetylation; D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival; D004261:DNA Replication; D051548:Histone Acetyltransferases / Q000172:deficiency / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000201:enzymology*; D060168:Thymocytes / Q000166:cytology / Q000378:metabolism
chemical_list: D006657:Histones; D016693:Receptors, Antigen, T-Cell, alpha-beta; D051548:Histone Acetyltransferases; C525638:Kat7 protein, mouse; D008239:Lysine
keywords: chromatin; epigenetic; histone aceytlation; immune