Department of Cellular Biotechnologies and Hematology, Faculty of Pharmacy and Medicine, Sapienza University of Rome, V.le Regina Elena 324, 00161 Rome, Italy.
Biochem J. 2012 Jan 15;441(2):645-52. doi: 10.1042/BJ20111417.
PARylation [poly(ADP-ribosyl)ation] is involved in the maintenance of genomic methylation patterns through its control of Dnmt1 [DNA (cytosine-5)-methyltransferase 1] activity. Our previous findings indicated that Ctcf (CCCTC-binding factor) may be an important player in key events whereby PARylation controls the unmethylated status of some CpG-rich regions. Ctcf is able to activate Parp1 [poly(ADP-ribose) polymerase 1], which ADP-ribosylates itself and, in turn, inhibits DNA methylation via non-covalent interaction between its ADP-ribose polymers and Dnmt1. By such a mechanism, Ctcf may preserve the epigenetic pattern at promoters of important housekeeping genes. The results of the present study showed Dnmt1 as a new protein partner of Ctcf. Moreover, we show that Ctcf forms a complex with Dnmt1 and PARylated Parp1 at specific Ctcf target sequences and that PARylation is responsible for the maintenance of the unmethylated status of some Ctcf-bound CpGs. We suggest a mechanism by which Parp1, tethered and activated at specific DNA target sites by Ctcf, preserves their methylation-free status.
聚（ADP-核糖）化[PARylation]通过其对 Dnmt1[DNA（胞嘧啶-5）-甲基转移酶 1]活性的控制，参与维持基因组甲基化模式。我们之前的研究结果表明，Ctcf（CCCTC 结合因子）可能是 PARylation 控制某些富含 CpG 区域未甲基化状态的关键事件中的重要参与者。Ctcf 能够激活 Parp1[聚（ADP-核糖）聚合酶 1]，Parp1 将自身 ADP-核糖基化，然后通过其 ADP-核糖聚合物与 Dnmt1 之间的非共价相互作用抑制 DNA 甲基化。通过这种机制，Ctcf 可以在重要管家基因的启动子处保持表观遗传模式。本研究的结果表明 Dnmt1 是 Ctcf 的一个新的蛋白质伴侣。此外，我们表明 Ctcf 在特定的 Ctcf 靶序列处与 Dnmt1 和 PARylated Parp1 形成复合物，并且 PARylation 负责维持一些 Ctcf 结合的 CpGs 的非甲基化状态。我们提出了一种机制，即 Parp1 通过 Ctcf 连接并在特定的 DNA 靶位点被激活，从而保持它们的无甲基化状态。
