Epigenetic regulation of left–right asymmetry by DNA methylation |
| |
| Authors: | Lu Wang Zhibin Liu Hao Lin Dongyuan Ma Qinghua Tao Feng Liu |
| |
| Institution: | 1. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China;2. University of Chinese Academy of Science, Beijing, China;3. MOE Key Laboratory of Protein Sciences, Tsinghua University School of Life Sciences, Beijing, China |
| |
| Abstract: | DNA methylation is a major epigenetic modification; however, the precise role of DNA methylation in vertebrate development is still not fully understood. Here, we show that DNA methylation is essential for the establishment of the left–right (LR) asymmetric body plan during vertebrate embryogenesis. Perturbation of DNA methylation by depletion of DNA methyltransferase 1 (dnmt1) or dnmt3bb.1 in zebrafish embryos leads to defects in dorsal forerunner cell (DFC) specification or collective migration, laterality organ malformation, and disruption of LR patterning. Knockdown of dnmt1 in Xenopus embryos also causes similar defects. Mechanistically, loss of dnmt1 function induces hypomethylation of the lefty2 gene enhancer and promotes lefty2 expression, which consequently represses Nodal signaling in zebrafish embryos. We also show that Dnmt3bb.1 regulates collective DFC migration through cadherin 1 (Cdh1). Taken together, our data uncover dynamic DNA methylation as an epigenetic mechanism to control LR determination during early embryogenesis in vertebrates. |
| |
| Keywords: | cell adhesion DNA methylation dorsal forerunner cells left– right asymmetry Nodal signaling |
|
|
