Epigenetic regulation of left–right asymmetry by
            <scp>DNA</scp>
            methylation

Wang, Lu; Liu, Zhibin; Lin, Haiyan; Ma, Dongyuan; Tao, Qinghua; Liu, Feng

doi:10.15252/embj.201796580

Cited by 25 publications

(17 citation statements)

References 52 publications

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“…Alternatively, coral methylomes could escape reprogramming in the presence of a segregated germline in a similar fashion to zebrafish paternal methylomes 38,39 . Transfer of paternal methylomes plays an important role in zebrafish embryogenesis, for example in guiding left-right asymmetry of organ positioning 40 . Importantly, in corals, inheritance of functional DNA methylation could enable acclimatory gains in stress tolerance accumulated during long colony lifespans to be transferred to large numbers of gametes or larvae (i.e.…”

Section: Figmentioning

confidence: 99%

Intergenerational epigenetic inheritance in reef-building corals

Liew

Howells

Wang

et al. 2018

Preprint

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MainThe notion that intergenerational or transgenerational inheritance operates solely through genetic means is slowly being eroded: epigenetic mechanisms have been shown to induce heritable changes in gene activity in plants 1,2 and metazoans 1,3. Inheritance of DNA methylation provides a potential pathway for environmentally induced phenotypes to contribute to evolution of species and populations 1–4. However, in basal metazoans, it is unknown whether inheritance of CpG methylation patterns occurs across the genome (as in plants) or as rare exceptions (as in mammals) 4. Here, we demonstrate genome-wide intergenerational transmission of CpG methylation patterns from parents to sperm and larvae in a reef-building coral. We also show variation in hypermethylated genes in corals from distinct environments, indicative of responses to variations in temperature and salinity. These findings support a role of DNA methylation in the transgenerational inheritance of traits in corals, which may extend to enhancing their capacity to adapt to climate change.

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Section: Figmentioning

confidence: 99%

Intergenerational epigenetic inheritance in reef-building corals

Liew

Howells

Wang

et al. 2018

Preprint

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“…Interestingly, we also observed an event of positive selection at the common ancestor of Primates and the flying lemur with LEFTY2, with which DNA methylation plays a critical role during early embryogenesis in vertebrates (Wang et al 2017), although the results need to be treated with caution.…”

Section: Potential Drivers Of Mammalian Pgrn Variationmentioning

confidence: 78%

Genetic signatures of evolution of the pluripotency gene regulating network across mammals

Endo

Kamei

Inoue‐Murayama

2020

Preprint

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Mammalian pluripotent stem cells (PSCs) have distinct molecular and biological characteristics, but we lack a comprehensive understanding of regulatory network evolution in mammals. Here, we applied a comparative genetic analysis of 134 genes constituting the pluripotency gene regulatory network across 48 mammalian species covering all the major taxonomic groups. We found evolutionary conservation in JAK-STAT and PI3K-Akt signaling pathways, suggesting equivalent capabilities in self-renewal and proliferation of mammalian PSCs. On the other hand, we discovered rapid evolution of the downstream targets of the core regulatory circuit, providing insights into variations of characteristics. Our data indicate that the variations in the PSCs characteristics may be due to positive selections in the downstream targets of the core regulatory circuit. We further reveal that positively selected genes can be associated with species unique adaptation that is not dedicated to regulation of PSCs. These results provide important insight into the evolution of the pluripotency gene regulatory network underlying variations in characteristics of mammalian PSCs.

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“…No differences were uncovered in the nucleotide sequences of the lft2 exons in cavefish of either sex, indicating that the lft2 coding region is intact. The decrease in lft2 expression during segmentation, but not during gastrulation, and the absence of coding mutations suggests that lft2 downregulation is controlled by cis-or trans-acting changes in regulatory regions or by epigenetic mechanisms [24][25][26] in cavefish. Lastly, to investigate the role of lft2 in heart laterality, surface fish with downregulated lft2 expression were produced by CRISPR-Cas9 editing.…”

Section: Role Of Lefty Genes In Cavefish Left-right Asymmetrymentioning

confidence: 99%

Evolutionary Changes in Left-Right Visceral Asymmetry inAstyanaxCavefish

Shi

et al. 2020

Preprint

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Vertebrates show conserved left-right (L-R) asymmetry of internal organs controlled by Nodal-Pitx2/Lefty signaling [1][2][3]. Modifications in L-R asymmetry occur in mutants [4] and rarely in humans [5], but little is known about natural L-R changes during evolution. Here we describe changes in L-R asymmetry in Astyanax mexicanus, a teleost with ancestral surface (surface fish) and derived cave (cavefish) morphs [6]. In teleosts, Nodal-Pitx2 signaling is activated in the left lateral plate mesoderm (LPM), the cardiac tube jogs to the left and loops to the right (D-looping), and the liver and pancreas form on opposite sides of the midline. Surface fish show conventional L-R patterning, but cavefish can show Nodal-Pitx2 expression in the right LPM or bilaterally, left (L)-looping hearts, and reversed liver and pancreas asymmetry, and these reversals have no effect on survival. The Lefty1 Nodal antagonist is expressed along the surface fish and cavefish midlines, but expression of the Lefty2 antagonist is absent in the LPM of most cavefish embryos, suggesting a role for lefty2 (lft2) in changing organ asymmetry. Although CRISPR-Cas9 lft2 editing affected D-looping in surface fish, the cavefish lft2 gene showed no coding mutations, and was expressed normally during cavefish gastrulation, suggesting downregulation by regulatory changes. Reciprocal hybridization, the fertilization of cavefish eggs with surface fish sperm and vice versa, indicated that the change in cavefish L-R asymmetry is a maternal genetic effect. Our studies reveal natural changes in internal organ asymmetry during evolution and introduce A. mexicanus as a new model to study the underlying mechanisms.

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Epigenetic regulation of left–right asymmetry by DNA methylation

Cited by 25 publications

References 52 publications

Intergenerational epigenetic inheritance in reef-building corals

Intergenerational epigenetic inheritance in reef-building corals

Genetic signatures of evolution of the pluripotency gene regulating network across mammals

Evolutionary Changes in Left-Right Visceral Asymmetry inAstyanaxCavefish

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