Russ Brendan E, Olshanksy Moshe, Smallwood Heather S, Li Jasmine, Denton Alice E, Prier Julia E, Stock Angus T, Croom Hayley A, Cullen Jolie G, Nguyen Michelle L T, Rowe Stephanie, Olson Matthew R, Finkelstein David B, Kelso Anne, Thomas Paul G, Speed Terry P, Rao Sudha, Turner Stephen J
Department of Microbiology and Immunology, The Doherty Institute at The University of Melbourne, Parkville, VIC 3010, Australia.
Department of Bioinformatics, Walter and Eliza Hall Institute, Parkville, VIC 3010, Australia.
Immunity. 2014 Nov 20;41(5):853-65. doi: 10.1016/j.immuni.2014.11.001. Epub 2014 Nov 6.
The molecular mechanisms that regulate the rapid transcriptional changes that occur during cytotoxic T lymphocyte (CTL) proliferation and differentiation in response to infection are poorly understood. We have utilized ChIP-seq to assess histone H3 methylation dynamics within naive, effector, and memory virus-specific T cells isolated directly ex vivo after influenza A virus infection. Our results show that within naive T cells, codeposition of the permissive H3K4me3 and repressive H3K27me3 modifications is a signature of gene loci associated with gene transcription, replication, and cellular differentiation. Upon differentiation into effector and/or memory CTLs, the majority of these gene loci lose repressive H3K27me3 while retaining the permissive H3K4me3 modification. In contrast, immune-related effector gene promoters within naive T cells lacked the permissive H3K4me3 modification, with acquisition of this modification occurring upon differentiation into effector/memory CTLs. Thus, coordinate transcriptional regulation of CTL genes with related functions is achieved via distinct epigenetic mechanisms.
在细胞毒性T淋巴细胞（CTL）响应感染而增殖和分化过程中发生的快速转录变化的分子机制仍知之甚少。我们利用染色质免疫沉淀测序（ChIP-seq）来评估甲型流感病毒感染后直接从体内分离出的初始、效应和记忆病毒特异性T细胞内组蛋白H3甲基化动态。我们的结果表明，在初始T细胞内，允许性的H3K4me3和抑制性的H3K27me3修饰的共沉积是与基因转录、复制和细胞分化相关的基因位点的一个特征。在分化为效应和/或记忆CTL后，这些基因位点中的大多数失去了抑制性的H3K27me3，同时保留了允许性的H3K4me3修饰。相反，初始T细胞内的免疫相关效应基因启动子缺乏允许性的H3K4me3修饰，在分化为效应/记忆CTL时才获得这种修饰。因此，通过不同的表观遗传机制实现了具有相关功能的CTL基因的协调转录调控。
