Similar Datasets
Project description:DNA methylation is a repressive epigenetic modification that is essential for development, exemplified by the embryonic and perinatal lethality observed in mice lacking de novo DNA methyltransferases (DNMTs). Here we characterise the role for DNMT3A, 3B and 3L in gene regulation and development of the mouse placenta. We demonstrate that each of the DNMTs is required to establish the placental methylome and is distinctly targeted to genome based on underlying chromatin features. Loss of Dnmt3b results in de-repression of germline genes in trophoblast lineages and impaired development of the placental maternal-foetal interface. Critically, loss of DNA methylation in the placenta did not lead to abnormalities in lineage specification or cell identity, but to defective formation and vascularisation of the placental labyrinth. Using Sox2-Cre to delete Dnmt3b in the embryo, leaving expression intact in placental trophoblast cells, we were able to rescue the placental phenotype and, consequently, the embryonic lethality, as Dnmt3b null embryos could now survive to birth. We conclude that the principal function of DNA methylation during embryogenesis is to regulate placental function, which in turn is critical for embryo survival.
2022-12-15 | GSE203292 | GEO
Project description:DNA methylation is a repressive epigenetic modification that is essential for development, exemplified by the embryonic and perinatal lethality observed in mice lacking de novo DNA methyltransferases (DNMTs). Here we characterise the role for DNMT3A, 3B and 3L in gene regulation and development of the mouse placenta. We demonstrate that each of the DNMTs is required to establish the placental methylome and is distinctly targeted to genome based on underlying chromatin features. Loss of Dnmt3b results in de-repression of germline genes in trophoblast lineages and impaired development of the placental maternal-foetal interface. Critically, loss of DNA methylation in the placenta did not lead to abnormalities in lineage specification or cell identity, but to defective formation and vascularisation of the placental labyrinth. Using Sox2-Cre to delete Dnmt3b in the embryo, leaving expression intact in placental trophoblast cells, we were able to rescue the placental phenotype and, consequently, the embryonic lethality, as Dnmt3b null embryos could now survive to birth. We conclude that the principal function of DNA methylation during embryogenesis is to regulate placental function, which in turn is critical for embryo survival.
2022-12-15 | GSE203458 | GEO
Project description:DNA methylation is a repressive epigenetic modification that is essential for development, exemplified by the embryonic and perinatal lethality observed in mice lacking de novo DNA methyltransferases (DNMTs). Here we characterise the role for DNMT3A, 3B and 3L in gene regulation and development of the mouse placenta. We demonstrate that each of the DNMTs is required to establish the placental methylome and is distinctly targeted to genome based on underlying chromatin features. Loss of Dnmt3b results in de-repression of germline genes in trophoblast lineages and impaired development of the placental maternal-foetal interface. Critically, loss of DNA methylation in the placenta did not lead to abnormalities in lineage specification or cell identity, but to defective formation and vascularisation of the placental labyrinth. Using Sox2-Cre to delete Dnmt3b in the embryo, leaving expression intact in placental trophoblast cells, we were able to rescue the placental phenotype and, consequently, the embryonic lethality, as Dnmt3b null embryos could now survive to birth. We conclude that the principal function of DNA methylation during embryogenesis is to regulate placental function, which in turn is critical for embryo survival.
2022-12-15 | GSE203291 | GEO
Project description:DNA methylation is a repressive epigenetic modification that is essential for development, exemplified by the embryonic and perinatal lethality observed in mice lacking de novo DNA methyltransferases (DNMTs). Here we characterise the role for DNMT3A, 3B and 3L in gene regulation and development of the mouse placenta. We demonstrate that each of the DNMTs is required to establish the placental methylome and is distinctly targeted to genome based on underlying chromatin features. Loss of Dnmt3b results in de-repression of germline genes in trophoblast lineages and impaired development of the placental maternal-foetal interface. Critically, loss of DNA methylation in the placenta did not lead to abnormalities in lineage specification or cell identity, but to defective formation and vascularisation of the placental labyrinth. Using Sox2-Cre to delete Dnmt3b in the embryo, leaving expression intact in placental trophoblast cells, we were able to rescue the placental phenotype and, consequently, the embryonic lethality, as Dnmt3b null embryos could now survive to birth. We conclude that the principal function of DNA methylation during embryogenesis is to regulate placental function, which in turn is critical for embryo survival.
2022-12-15 | GSE203226 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-03-19 | GSE150072 | GEO
Project description:Mammalian DNA methylation patterns are established by two de novo DNA methyltransferases, DNMT3A and DNMT3B, which exhibit both redundant and distinctive methylation activities. However, the related molecular basis remains undetermined. Through comprehensive structural, enzymology and cellular characterization of DNMT3A and DNMT3B, we here report a multi-layered substrate-recognition mechanism underpinning their divergent genomic methylation activities. A hydrogen bond in the catalytic loop of DNMT3B causes a lower CpG specificity than DNMT3A, while the interplay of target recognition domain and homodimeric interface fine-tunes the distinct target selection between the two enzymes, with Lysine 777 of DNMT3B acting as a unique sensor of the +1 flanking base. The divergent substrate preference between DNMT3A and DNMT3B provides an explanation for site-specific epigenomic alterations seen in ICF syndrome with DNMT3B mutations. Together, this study reveals distinctive substrate-readout mechanisms of the two DNMT3 enzymes, implicative of their differential roles during development and pathogenesis.
| S-EPMC7335073 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-02-13 | GSE114335 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-04-14 | GSE99694 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-04-02 | E-GEOD-66911 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-03-02 | GSE167955 | GEO