Essential role for the histone acetyltransferase KAT7 in T cell development, fitness, and survival

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

Thomas, Tim¹  Allan, Rhys S.²  Voss, Anne K.² 

[1] and..Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia;The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia

关键词: immune;    chromatin;    epigenetic;    histone aceytlation;   

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

CC BY