Essential role for the histone acetyltransferase KAT7 in T cell development, fitness, and survival
- Author(s)
- Newman, DM; Voss, AK; Thomas, T; Allan, RS;
- Journal Title
- J Leukoc Biol
- Publication Type
- Journal Article in press
- 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 alphabeta 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.
- Publisher
- Society for Leukocyte Biology
- Research Division(s)
- Development And Cancer; Molecular Immunology
- PubMed ID
- 27733580
- Publisher's Version
- https://doi.org/10.1189/jlb.1MA0816-338R
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2016-10-19 11:52:31
Last Modified: 2016-10-19 12:46:15