Gamma Interferon-Dependent Transcriptional Memory via Relocalization of a Gene Locus to PML Nuclear Bodies
Gamma Interferon-Dependent Transcriptional Memory via Relocalization of a Gene Locus to PML Nuclear Bodies
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DOI：
10.1128/mcb.00906-09
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发表时间：
2010-04-15
影响因子：
5.3
通讯作者：
Papamatheakis, Joseph
中科院分区：
文献类型：
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作者：
Gialitakis, Manolis;Arampatzi, Panagiota;Papamatheakis, Joseph
对过去细胞反应的记忆是对重复环境刺激的重要适应。我们解决了γ干扰素（IFN-γ）诱导的转录是否产生记忆，使细胞对第二刺激敏感的问题。我们已经发现，主要组织相容性复合体II类基因的IFN-γ诱导后，重新定位到早幼粒细胞白血病（PML）核小体，这种拓扑结构保持转录关闭后很长一段时间。PML蛋白与混合谱系白血病的同时相互作用在以高启动子组蛋白H3 K4二甲基化为特征的p53基因上产生了延长的容许染色质状态，其促进了再刺激后的快速表达。我们提出，主要的信号诱导的转录产生的空间和表观遗传的记忆，是通过几代细胞保持，并赋予细胞增加响应未来的激活信号。
Memory of past cellular responses is an essential adaptation to repeating environmental stimuli. We addressed the question of whether gamma interferon (IFN-gamma)-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-gamma, 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.