Mechanisms Of Transcriptional Regulation in Memory lymphocyte Response and Aging

记忆淋巴细胞反应和衰老的转录调控机制

• 批准号: 8335921
• 负责人: Nan ping Peter Weng
• 金额: $ 11.5万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8335921
• 关键词: Adult; Age; Aging; Antibodies; Antigens; CD28 gene; CD3 Antigens; CD8-Positive T-Lymphocytes; CD8B1 gene; Cell physiology; Cells; Chromatin; Exhibits; Gene Expression; Genes; Genetic Transcription; Goals; Histones; Hour; Immune response; In Vitro; Lymphocyte; Memory; Methods; Methylation; MicroRNAs; Pattern; Post-Transcriptional Regulation; Process; Role; T memory cell; T-Lymphocyte; Tissue-Specific Gene Expression; Transcriptional Regulation; base; cell type; comparative; histone modification; interest; response; trend

Memory T lymphocytes are characterized by their ability to exhibit a rapid response to the recall antigen. Our previous study shows that histone methylation provides a chromatin basis for the rapid transcriptional response of memory CD8 T cells. To further understand how the histone methylation patterns are established and maintained in memory T cells, we conducted a parallel analysis of gene expression changes with histone methylation changes in nave and memory (central and effector memory cells) CD8 T cells after in vitro stimulation. Nave, central memory and effector memory CD8 T cells were isolated from normal adult and stimulated in vitro with antibodies against CD3 and CD28. Gene expression changes were analyzed by microarray and histone methylation (H3K4me3 and H3K27me3) was analyzed by ChIP-Seq. As expected, we observed substantial changes in gene expression (25% increase and 25% decrease of total expressed genes) after 72 hours of stimulation, activation. In parallel, we observed similar trend of histone methylation (H3K4me3 and H3K27me3) changes in corresponding genes in CD8 T cells. Furthermore, we found that the open chromatin of some poised genes in memory CD8 T cells were established in activated nave CD8 T cells, suggesting that activation is a necessary step of convert the memory cell type of chromatin in nave cells. Together, these results indicate that histone methylation is dynamic after activation in CD8 T cells and suggest that activation-induced change of chromatin in nave T cells is part of differentiation process to establish memory T cells.

记忆T淋巴细胞的特征是它们对回忆抗原的快速反应能力。 我们先前的研究表明，组蛋白甲基化为记忆CD8 T细胞的快速转录反应提供了染色质基础。为了进一步了解如何在记忆T细胞中建立和维持组蛋白甲基化模式，我们对基因表达的平行分析在体外刺激后随着组蛋白甲基化的变化而随着组蛋白甲基化的变化而变化（中心和效应记忆细胞）CD8 T细胞。从正常成年人中分离出中殿，中央记忆和效应记忆CD8 T细胞，并用抗CD3和CD28的抗体在体外刺激。 通过微阵列分析基因表达变化，组蛋白甲基化（H3K4ME3和H3K27ME3）通过CHIP-SEQ分析。 正如预期的那样，我们观察到72小时刺激后，基因表达（增加25％和总数表达基因的降低25％，降低了25％）。 同时，我们观察到了组蛋白甲基化（H3K4ME3和H3K27ME3）的相似趋势在CD8 T细胞中相应基因的变化。此外，我们发现在活化的中含CD8 T细胞中建立了记忆CD8 T细胞中某些固定基因的开放染色质，这表明激活是转化中殿细胞中染色质的记忆细胞类型的必要步骤。 总之，这些结果表明，在CD8 T细胞中激活后，组蛋白甲基化是动态的，并表明激活诱导的中殿T细胞中染色质的变化是建立记忆T细胞的分化过程的一部分。