SOG1 activator and MYB3R repressors regulate a complex DNA damage network in Arabidopsis
SOG1 activator and MYB3R repressors regulate a complex DNA damage network in Arabidopsis
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DOI：
10.1073/pnas.1810582115
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发表时间：
2018-12-26
影响因子：
11.1
通讯作者：
Law, Julie A.
中科院分区：
文献类型：
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作者：
Bourbousse, Clara;Vegesna, Neeraja;Law, Julie A.
为了对抗DNA损伤，生物体会产生DNA损伤反应（DDR），导致细胞周期调节，DNA修复，在严重的情况下，细胞死亡。强调基因调控在这种反应中的重要性，在拟南芥中的研究已经证明，所有上述过程都依赖于γ反应的供应者1（SOG 1），一种NAC家族转录因子（TF），在功能上等同于哺乳动物肿瘤抑制因子p53。然而，将SOG 1连接到这些过程的表达网络在很大程度上仍然未知，尽管DDR跨度从几分钟到几小时，但大多数转录组数据对应于单个时间点快照。在这里，我们产生的转录模型的DDR从伽马（gamma）照射的野生型和sog 1幼苗在24小时的时间过程中使用DREM，动态调控事件矿工，揭示了11个共表达的基因组具有不同的生物功能和顺式调控功能。在这些网络中，额外的染色质免疫沉淀和转录组学实验显示，SOG 1是主要的激活剂，直接靶向最强烈的上调基因，包括TF，修复因子和早期细胞周期调节因子，而三个MYB 3R TF是主要的阻遏物，特异性靶向最强烈的下调基因，主要对应于G2/M细胞周期调节基因。这些模型共同揭示了由γ辐射引发的转录事件的时间动态，并将这些事件与TF和生物过程在与响应DNA损伤的关键过程相协调的时间尺度上相关联，极大地扩展了我们对DDR的理解。
To combat DNA damage, organisms mount a DNA damage response (DDR) that results in cell cycle regulation, DNA repair and, in severe cases, cell death. Underscoring the importance of gene regulation in this response, studies in Arabidopsis have demonstrated that all of the aforementioned processes rely on SUPPRESSOR OF GAMMA RESPONSE 1 (SOG1), a NAC family transcription factor (TF) that has been functionally equated to the mammalian tumor suppressor, p53. However, the expression networks connecting SOG1 to these processes remain largely unknown and, although the DDR spans from minutes to hours, most transcriptomic data correspond to single timepoint snapshots. Here, we generated transcriptional models of the DDR fromGAMMA (gamma)-irradiated wild-type and sog1 seedlings during a 24-hour time course using DREM, the Dynamic Regulatory Events Miner, revealing 11 coexpressed gene groups with distinct biological functions and cis-regulatory features. Within these networks, additional chromatin immunoprecipitation and transcriptomic experiments revealed that SOG1 is the major activator, directly targeting the most strongly up-regulated genes, including TFs, repair factors, and early cell cycle regulators, while three MYB3R TFs are the major repressors, specifically targeting the most strongly down-regulated genes, which mainly correspond to G2/M cell cycle-regulated genes. Together these models reveal the temporal dynamics of the transcriptional events triggered by gamma-irradiation and connects these events to TFs and biological processes over a time scale commensurate with key processes coordinated in response to DNA damage, greatly expanding our understanding of the DDR.