Institut de Recherche Thérapeutique de l'Université de Nantes, INSERM U892, Centre de Recherche en Cancérologie Nantes-Angers, Equipe Apoptose et Progression Tumorale, 8 quai moncousu, BP7021, 44007 Nantes, France.
Cell Div. 2012 Feb 20;7:5. doi: 10.1186/1747-1028-7-5.
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.
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.
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.
在哺乳动物基因组的细胞分裂过程中,谱系特异性 DNA 甲基化模式的克隆传递是一个主要由 DNA 甲基转移酶 Dnmt1 控制的关键生物学过程。为了研究细胞周期中 DNA 甲基化遗传的可能动态机制,我们使用邻近连接原位检测(P-LISA)来分析 Dnmt1 包含复合物的形成和 DNA 募集的动力学。
P-LISA、顺序染色质免疫沉淀和定量甲基化特异性 PCR 表明,Dnmt1/PCNA/UHRF1 包含复合物主要在细胞周期的 S 期形成并募集在 DNA 上,而几个 Dnmt1/转录因子包含复合物的形成和 DNA 募集与 S 期无关,但与 G0/G1 和/或 G2/M 期有关。
我们的数据证实了 DNA 甲基化遗传发生在 S 期,并表明 DNA 甲基化遗传也可以发生在细胞周期的 G0/G1 和 G2/M 期。