Project description:Decades of work in placental (eutherian) species have constructed a paradigm of mammalian development, wherein the genome-wide erasure of parental DNA methylation is required for embryogenesis1-10. Whether such DNA methylation reprogramming is, in fact, conserved in other mammals is unknown. To resolve this point, we generated base-resolution DNA methylation maps in gametes, embryos and adult tissues of the opossum marsupial Monodelphis domestica, revealing extensive variations from the eutherian-derived model. In stark contrast with eutherians, the marsupial genome remains hypermethylated during the cleavage stages and in the embryo proper of the blastocyst. In the extra-embryonic trophectoderm DNA methylation is reduced, suggesting an important evolutionary conserved function for DNA hypomethylation in formation of the mammalian placenta. Furthermore, unlike in eutherians, the inactive X chromosome becomes globally DNA hypomethylated during embryogenesis. Using our DNA methylation profiles, we identify a candidate mechanism for imprinted X-inactivation in marsupials, via maternal promoter DNA methylation of the Xist-like non-coding RNA RSX11. How mammalian embryos employ DNA methylation to regulate their development is therefore more mechanistically diverse than current models can accommodate.
Project description:Decades of work in placental (eutherian) species have constructed a paradigm of mammalian development, wherein the genome-wide erasure of parental DNA methylation is required for embryogenesis1-10. Whether such DNA methylation reprogramming is, in fact, conserved in other mammals is unknown. To resolve this point, we generated base-resolution DNA methylation maps in gametes, embryos and adult tissues of the opossum marsupial Monodelphis domestica, revealing extensive variations from the eutherian-derived model. In stark contrast with eutherians, the marsupial genome remains hypermethylated during the cleavage stages and in the embryo proper of the blastocyst. In the extra-embryonic trophectoderm DNA methylation is reduced, suggesting an important evolutionary conserved function for DNA hypomethylation in formation of the mammalian placenta. Furthermore, unlike in eutherians, the inactive X chromosome becomes globally DNA hypomethylated during embryogenesis. Using our DNA methylation profiles, we identify a candidate mechanism for imprinted X-inactivation in marsupials, via maternal promoter DNA methylation of the Xist-like non-coding RNA RSX11. How mammalian embryos employ DNA methylation to regulate their development is therefore more mechanistically diverse than current models can accommodate.
Project description:Decades of work in placental (eutherian) species have constructed a paradigm of mammalian development, wherein the genome-wide erasure of parental DNA methylation is required for embryogenesis1-10. Whether such DNA methylation reprogramming is, in fact, conserved in other mammals is unknown. To resolve this point, we generated base-resolution DNA methylation maps in gametes, embryos and adult tissues of the opossum marsupial Monodelphis domestica, revealing extensive variations from the eutherian-derived model. In stark contrast with eutherians, the marsupial genome remains hypermethylated during the cleavage stages and in the embryo proper of the blastocyst. In the extra-embryonic trophectoderm DNA methylation is reduced, suggesting an important evolutionary conserved function for DNA hypomethylation in formation of the mammalian placenta. Furthermore, unlike in eutherians, the inactive X chromosome becomes globally DNA hypomethylated during embryogenesis. Using our DNA methylation profiles, we identify a candidate mechanism for imprinted X-inactivation in marsupials, via maternal promoter DNA methylation of the Xist-like non-coding RNA RSX11. How mammalian embryos employ DNA methylation to regulate their development is therefore more mechanistically diverse than current models can accommodate.
Project description:During development, the inherited DNA methylation patterns from the parental gametes needs to be remodeled into a state compatible with embryonic pluripotency. In Zebrafish, this remodeling is achieved by the maternal methylome becoming hypomethylated to match the paternal methylome. However, how this is achieved in medaka (another teleost fish) is currently not known. Moreover, how DNA methylation remodeling is impacted in hybrid organisms, and the effects this may have on their development, is also not known. Here we address these questions by generation whole genome bisulfite sequencing data for zebrafish, medaka and zebrafish medaka embryos.
Project description:Decades of work in placental (eutherian) species have constructed a paradigm of mammalian development, wherein the genome-wide erasure of parental DNA methylation is required for embryogenesis1-10. Whether such DNA methylation reprogramming is, in fact, conserved in other mammals is unknown. To resolve this point, we generated base-resolution DNA methylation maps in gametes, embryos and adult tissues of the opossum marsupial Monodelphis domestica, revealing extensive variations from the eutherian-derived model. In stark contrast with eutherians, the marsupial genome remains hypermethylated during the cleavage stages and in the embryo proper of the blastocyst. In the extra-embryonic trophectoderm DNA methylation is reduced, suggesting an important evolutionary conserved function for DNA hypomethylation in formation of the mammalian placenta. Furthermore, unlike in eutherians, the inactive X chromosome becomes globally DNA hypomethylated during embryogenesis. Using our DNA methylation profiles, we identify a candidate mechanism for imprinted X-inactivation in marsupials, via maternal promoter DNA methylation of the Xist-like non-coding RNA RSX11. How mammalian embryos employ DNA methylation to regulate their development is therefore more mechanistically diverse than current models can accommodate.
Project description:We exposed zebrafish embryos to 0.3, 3, and 30 ppb (µg/L) of ATZ for 72 hours post fertilization. We performed whole-genome bisulfite sequencing (WGBS) to assess the effects of developmental ATZ exposure on DNA methylation in female fish brains
Project description:DNA methylation is an important epigenetic modification that undergoes dynamic changes in mammalian embryogenesis, during which both parental genomes are reprogrammed. Despite the many immunostaining studies that have assessed global methylation, the gene-specific DNA methylation patterns in bovine preimplantation embryos are unknown. Using reduced representation bisulfite sequencing, we determined genome-scale DNA methylation patterns of bovine sperm and individual in vivo developed oocytes and preimplantation embryos. We show that: 1) the major wave of genome-wide demethylation was completed by the 8-cell stage; 2) promoter methylation was significantly and inversely correlated with gene expression at the 8-cell and blastocyst stages; 3) sperm and oocytes have numerous differentially methylated regions (DMRs) - DMRs specific for sperm were strongly enriched in long terminal repeats (LTRs) and rapidly lost methylation in embryos, while the oocyte-specific DMRs were more frequently localized in exons and CpG islands (CGIs) and demethylated gradually across cleavage stages; 4) a unique set of DMRs were found between in vivo and in vitro matured oocytes; and 5) differential methylation between bovine gametes was confirmed in some but not all known imprinted genes. Our data provide insights into deciphering the complex epigenetic reprogramming of bovine early embryos and will serve as an important model for investigating human development and the evolutionary and regulatory roles of DNA methylation.