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Gamma Interferon-Dependent Transcriptional Memory via Relocalization of a Gene Locus to PML Nuclear Bodies

机译:通过基因位点重新定位到PML核体的γ干扰素依赖性转录记忆。

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Memory of past cellular responses is an essential adaptation to repeating environmental stimuli. We addressed the question of whether gamma interferon (IFN-γ)-inducible transcription generates memory that sensitizes cells to a second stimulus. We have found that the major histocompatibility complex class II gene DRA is relocated to promyelocytic leukemia (PML) nuclear bodies upon induction with IFN-γ, and this topology is maintained long after transcription shut off. Concurrent interaction of PML protein with mixed-lineage leukemia generates a prolonged permissive chromatin state on the DRA gene characterized by high promoter histone H3 K4 dimethylation that facilitates rapid expression upon restimulation. We propose that the primary signal-induced transcription generates spatial and epigenetic memory that is maintained through several cell generations and endows the cell with increased responsiveness to future activation signals.
机译:记忆过去的细胞反应是对重复环境刺激的基本适应。我们解决了γ干扰素(IFN-γ)诱导的转录是否产生使细胞对第二种刺激敏感的记忆的问题。我们已经发现,主要的组织相容性复合物II类基因 DRA 在被IFN-γ诱导后被重新定位到早幼粒细胞白血病(PML)核体,并且这种拓扑结构在转录关闭后仍保持了很长时间。 PML蛋白与混合谱系白血病的并发相互作用在 DRA 基因上产生了延长的染色质状态,其特征在于高启动子组蛋白H3 K4的二甲基化,从而促进了再刺激时的快速表达。我们提出主要信号诱导的转录产生空间和表观遗传记忆,该记忆和遗传记忆通过多个细胞世代得以维持,并赋予细胞对未来激活信号增强的响应能力。

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