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.
journal_name
J Leukoc Bioljournal_title
Journal of leukocyte biologyauthors
Newman DM,Voss AK,Thomas T,Allan RSdoi
10.1189/jlb.1MA0816-338Rsubject
Has Abstractpub_date
2017-04-01 00:00:00pages
887-892issue
4eissn
0741-5400issn
1938-3673pii
jlb.1MA0816-338Rjournal_volume
101pub_type
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