PUBLICATION

Epigenetic regulation of left-right asymmetry by DNA methylation

Authors
Wang, L., Liu, Z., Lin, H., Ma, D., Tao, Q., Liu, F.
ID
ZDB-PUB-170909-7
Date
2017
Source
The EMBO journal   36(20): 2987-2997 (Journal)
Registered Authors
Liu, Feng, Liu, Zhibin, Ma, Dongyuan, Wang, Lu
Keywords
DNA methylation, Nodal signaling, cell adhesion, dorsal forerunner cells, left–right asymmetry
MeSH Terms
  • Animals
  • DNA Methylation*
  • Epigenesis, Genetic*
  • Gene Expression Regulation, Developmental*
  • Methyltransferases/metabolism
  • Xenopus/embryology*
  • Zebrafish/embryology*
PubMed
28882847 Full text @ EMBO J.
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.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Errata and Notes