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Kinetics of DNA methylation inheritance by the Dnmt1-including complexes during the cell cycle

机译:Dnmt1包括复合物在细胞周期中DNA甲基化遗传的动力学

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Background The clonal transmission of lineage-specific DNA methylation patterns in a mammalian genome during the cellular division is a crucial biological process controlled by the DNA methyltransferase Dnmt1, mainly. To investigate possible dynamic mechanisms of DNA methylation inheritance during the cell cycle, we used a Proximity Ligation In Situ Assay (P-LISA) to analyze the kinetic of formation and DNA recruitment of Dnmt1-including complexes. Results P-LISA, sequential chromatin immunoprecipitation and quantitative methylation specific PCR revealed that the Dnmt1/PCNA/UHRF1-including complexes are mainly formed and recruited on DNA during the S-phase of cell cycle, while the formation and the DNA recruitment of several Dnmt1/transcription factors-including complexes are not S-phase dependent but are G0/G1 and/or G2/M phases dependent. Conclusion Our data confirm that DNA methylation inheritance occurs in S-phase, and demonstrate that DNA methylation inheritance can also occur in G0/G1 and G2/M phases of the cell cycle.
机译:背景技术在细胞分裂期间,哺乳动物基因组中谱系特异性DNA甲基化模式的克隆传递主要是受DNA甲基转移酶Dnmt1控制的关键生物学过程。为了研究细胞周期内DNA甲基化遗传的可能动力学机制,我们使用了邻近结扎原位分析(P-LISA)来分析Dnmt1包括复合物的形成动力学和DNA募集。结果P-LISA,连续染色质免疫沉淀和定量甲基化特异性PCR表明,包括Dnmt1 / PCNA / UHRF1在内的复合物主要在细胞周期的S期形成并募集到DNA上,而多个Dnmt1的形成和募集到DNA上/转录因子(包括复合物)与S相无关,而与G0 / G1和/或G2 / M相有关。结论我们的数据证实DNA甲基化遗传发生在S期,并且证明DNA甲基化遗传也可以发生在细胞周期的G0 / G1和G2 / M期。

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