20 research outputs found

    Hijacking of transcriptional condensates by endogenous retroviruses

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    Most endogenous retroviruses (ERVs) in mammals are incapable of retrotransposition; therefore, why ERV derepression is associated with lethality during early development has been a mystery. Here, we report that rapid and selective degradation of the heterochromatin adapter protein TRIM28 triggers dissociation of transcriptional condensates from loci encoding super-enhancer (SE)-driven pluripotency genes and their association with transcribed ERV loci in murine embryonic stem cells. Knockdown of ERV RNAs or forced expression of SE-enriched transcription factors rescued condensate localization at SEs in TRIM28-degraded cells. In a biochemical reconstitution system, ERV RNA facilitated partitioning of RNA polymerase II and the Mediator coactivator into phase-separated droplets. In TRIM28 knockout mouse embryos, single-cell RNA-seq analysis revealed specific depletion of pluripotent lineages. We propose that coding and noncoding nascent RNAs, including those produced by retrotransposons, may facilitate ‘hijacking’ of transcriptional condensates in various developmental and disease contexts

    Spatiotemporal transcriptomic maps of whole mouse embryos at the onset of organogenesis

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    Spatiotemporal orchestration of gene expression is required for proper embryonic development. The use of single-cell technologies has begun to provide improved resolution of early regulatory dynamics, including detailed molecular definitions of most cell states during mouse embryogenesis. Here we used Slide-seq to build spatial transcriptomic maps of complete embryonic day (E) 8.5 and E9.0, and partial E9.5 embryos. To support their utility, we developed sc3D, a tool for reconstructing and exploring three-dimensional ‘virtual embryos’, which enables the quantitative investigation of regionalized gene expression patterns. Our measurements along the main embryonic axes of the developing neural tube revealed several previously unannotated genes with distinct spatial patterns. We also characterized the conflicting transcriptional identity of ‘ectopic’ neural tubes that emerge in Tbx6 mutant embryos. Taken together, we present an experimental and computational framework for the spatiotemporal investigation of whole embryonic structures and mutant phenotypes

    Dynamic antagonism between key repressive pathways maintains the placental epigenome

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    DNA and Histone 3 Lysine 27 methylation typically function as repressive modifications and operate within distinct genomic compartments. In mammals, the majority of the genome is kept in a DNA methylated state, whereas the Polycomb repressive complexes regulate the unmethylated CpG-rich promoters of developmental genes. In contrast to this general framework, the extra-embryonic lineages display non-canonical, globally intermediate DNA methylation levels, including disruption of local Polycomb domains. Here, to better understand this unusual landscape’s molecular properties, we genetically and chemically perturbed major epigenetic pathways in mouse trophoblast stem cells. We find that the extra-embryonic epigenome reflects ongoing and dynamic de novo methyltransferase recruitment, which is continuously antagonized by Polycomb to maintain intermediate, locally disordered methylation. Despite its disorganized molecular appearance, our data point to a highly controlled equilibrium between counteracting repressors within extra-embryonic cells, one that can seemingly persist indefinitely without bistable features typically seen for embryonic forms of epigenetic regulation

    E9.0_Embryo.h5ad

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    3D registered E9.0 embryo for sc3D-visualizer</p

    E8.5_Embryo2.h5ad

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    3D registered data of E8.5 Embryo_2 for sc3D-visualizer</p

    E8.5_Embryo1.h5ad

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    3D registered data of E8.5 embryo_1 for sc3D-visualizer</p

    Effect of Microstructure on Roll-Ability and Shape Memory Effect in Cu-Based Shape Memory Alloys

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    29-37Ternary Cu-12Al-4Mn and Cu-12Al-4Ni have been chosen for the present study and different alloying elements have been added in an attempt to further improve upon the shape memory properties in terms of the desired microstructure in the quenched condition. It has been observed that all compositions do not exhibit the martensitic structure on quenching and different types of martensitic phases are exhibited depending on the alloying constituents. Attempts have been made to roll the samples into thin sheets through multiple passes. It has been found that although the ternary base alloys can easily be rolled the quaternary alloys with both Mn and Ni make the sample brittle rendering it unsuitable for rolling. Also adding of Zn and Mg has not exhibited the desired microstructure for exhibiting the shape memory properties and also could not be rolled though these samples were not brittle. The ease of roll-ability has been compared between the alloys and correlated with the microstructure which helps in understanding which type of martensitic phase is useful in rolling the samples

    Effect of Microstructure on Roll-Ability and Shape Memory Effect in Cu-Based Shape Memory Alloys

    No full text
    Ternary Cu-12Al-4Mn and Cu-12Al-4Ni have been chosen for the present study and different alloying elements have been added in an attempt to further improve upon the shape memory properties in terms of the desired microstructure in the quenched condition. It has been observed that all compositions do not exhibit the martensitic structure on quenching and different types of martensitic phases are exhibited depending on the alloying constituents. Attempts have been made to roll the samples into thin sheets through multiple passes. It has been found that although the ternary base alloys can easily be rolled the quaternary alloys with both Mn and Ni make the sample brittle rendering it unsuitable for rolling. Also adding of Zn and Mg has not exhibited the desired microstructure for exhibiting the shape memory properties and also could not be rolled though these samples were not brittle. The ease of roll-ability has been compared between the alloys and correlated with the microstructure which helps in understanding which type of martensitic phase is useful in rolling the samples

    Dual-Gate Self-Aligned a-IGZO TFTs using 5-Mask Steps

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    © 2015 Society for Information Display. We report a dual-gate (DG) self-aligned (SA) a-IGZO TFT process that comprises only five mask steps. The top-gate (TG) is self-aligned (SA) which enables the high speed operation. The secondary bottom-gate (BG) enables to improve parameters such as on-current (ION) and the sub-threshold slope (SS -1 ) substantially when both gates are connected together.status: publishe
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