Inducible chromatin priming is associated with the establishment of immunological memory in T cells.
Inducible chromatin priming is associated with the establishment of immunological memory in T cells.
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DOI：
10.15252/embj.201592534
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发表时间：
2016-03-01
期刊：
影响因子：
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通讯作者：
Cockerill PN
中科院分区：
文献类型：
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作者：
Bevington SL;Cauchy P;Piper J;Bertrand E;Lalli N;Jarvis RC;Gilding LN;Ott S;Bonifer C;Cockerill PN
免疫记忆是脊椎动物生理学的一个决定性特征，它允许对重复感染做出快速反应。然而，其建立和维持所需的分子机制仍然知之甚少。在这里，我们证明了获得T细胞记忆的第一步发生在naïve T细胞通过抗原刺激的初始激活阶段。这一事件引发了广泛的染色质重塑，将免疫反应基因重编程为稳定维持的启动状态，在最终分化之前。激活诱导转录因子NFAT和AP‐1产生数千个新的dna酶I -超敏感位点（DHSs），使ETS‐1和RUNX1能够招募到以前无法进入的位点。值得注意的是，这些dhs在激活停止后很长一段时间保持稳定，在复制后被保存，并在记忆表型细胞中维持。我们发现，引物dhs维持了诱导基因和调节免疫反应的增强子附近的活性染色质区域。我们认为，这种启动机制可能通过促进在先前激活的T细胞中诱导附近的可诱导调节元件来促进T细胞的免疫记忆。
Immunological memory is a defining feature of vertebrate physiology, allowing rapid responses to repeat infections. However, the molecular mechanisms required for its establishment and maintenance remain poorly understood. Here, we demonstrated that the first steps in the acquisition of T‐cell memory occurred during the initial activation phase of naïve T cells by an antigenic stimulus. This event initiated extensive chromatin remodeling that reprogrammed immune response genes toward a stably maintained primed state, prior to terminal differentiation. Activation induced the transcription factors NFAT and AP‐1 which created thousands of new DNase I‐hypersensitive sites (DHSs), enabling ETS‐1 and RUNX1 recruitment to previously inaccessible sites. Significantly, these DHSs remained stable long after activation ceased, were preserved following replication, and were maintained in memory‐phenotype cells. We show that primed DHSs maintain regions of active chromatin in the vicinity of inducible genes and enhancers that regulate immune responses. We suggest that this priming mechanism may contribute to immunological memory in T cells by facilitating the induction of nearby inducible regulatory elements in previously activated T cells.