Kim Jeong Do, Kang Keunsoo, Kim Joomyeong
Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA.
Nucleic Acids Res. 2009 Sep;37(17):5656-64. doi: 10.1093/nar/gkp613. Epub 2009 Jul 23.
Unusual clusters of YY1 binding sites are located within several differentially methylated regions (DMRs), including Xist, Nespas and Peg3, which all become methylated during oogenesis. In this study, we performed conditional YY1 knockdown (KD) to investigate YY1's roles in DNA methylation of these DMRs. Reduced levels of YY1 during spermatogenesis did not cause any major change in these DMRs although the same YY1 KD caused hypermethylation in these DMRs among a subset of aged mice. However, YY1 KD during oogenesis resulted in the loss of DNA methylation on Peg3 and Xist, but there were no changes on Nespas and H19. Continued YY1 KD from oogenesis to the blastocyst stage caused further loss in DNA methylation on Peg3. Consequently, high incidents of lethality were observed among embryos that had experienced the reduced levels of YY1 protein. Overall, the current study suggests that YY1 likely plays a role in the de novo DNA methylation of the DMRs of Peg3 and Xist during oogenesis and also in the maintenance of unmethylation status of these DMRs during spermatogenesis.
YY1结合位点的异常簇位于几个差异甲基化区域（DMR）内，包括Xist、Nespas和Peg3，这些区域在卵子发生过程中都会发生甲基化。在本研究中，我们进行了条件性YY1敲低（KD）以研究YY1在这些DMR的DNA甲基化中的作用。精子发生过程中YY1水平降低并未导致这些DMR发生任何重大变化，尽管相同的YY1敲低在一部分老年小鼠中导致这些DMR发生高甲基化。然而，卵子发生过程中的YY1敲低导致Peg3和Xist上的DNA甲基化缺失，但Nespas和H19没有变化。从卵子发生到囊胚阶段持续进行YY1敲低导致Peg3上的DNA甲基化进一步缺失。因此，在经历了YY1蛋白水平降低的胚胎中观察到高致死率。总体而言，当前研究表明，YY1可能在卵子发生过程中Peg3和Xist的DMR的从头DNA甲基化中发挥作用，并且在精子发生过程中也参与维持这些DMR的未甲基化状态。
