Molecular mapping of nuclear lamina interactions in the mammalian embryo reveals de novo establishment of nuclear architecture
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ABSTRACT:
PROVIDER: PRJNA448167 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6920840.fastq.gz | Fastqsanger.gz | |||
| SRR6920950.fastq.gz | Fastqsanger.gz | |||
| SRR6920960.fastq.gz | Fastqsanger.gz | |||
| SRR6920970.fastq.gz | Fastqsanger.gz | |||
| SRR6920980.fastq.gz | Fastqsanger.gz |
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Project description:We generated high-resolution maps of genome-lamina interactions for different stages of the pre-implantation mouse embryo, including oocyte, zygote, 2cell stage and 8cell stage and additionally mouse ES cells. We find that LAD domains are already present at the zygote stage, but not in the oocyte, concluding that genome-nuclear lamina interactions are not inherited from the maternal germline, but instead are established de novo rapidly after fertilisation. By using a hybrid genetic background, we were able to identify parental-specific genome-nuclear lamina interaction, allowing us to show that the parental genomes have different features, which are globally resolved at the 8-cell stage. We blocked replication in zygotes by treatment with aphidicolin and found that LAD establishment was unaffected. Moreover, we ectopically expressed Kdm5b in zygotes and show that paternal LAD formation is impaired, suggesting that this mechanism is dependent upon de novo H3K4 methylation. Altogether, our data suggest a step-wise assembly model whereby early LAD formation precedes consolidation of TADs and reveals non-inheritance of nuclear organisation from the germline.
2019-03-13 | GSE112551 | GEO
Project description:The nuclear lamina is a proteinaceous network of filaments that provide both structural and gene regulatory functions by tethering proteins and large domains of DNA, so-called lamin associated domains (LADs), to the periphery of the nucleus. LADs are a large fraction of the mammalian genome that are repressed, in part, by their association to the nuclear periphery. The genesis and maintenance of LADs is poorly understood as are the proteins that participate in these functions. In an effort to identify proteins that reside at the nuclear periphery and potentially interact with LADs, we have taken a two-pronged approach. First, we have undertaken an interactome analysis of the inner nuclear membrane bound LAP2β to further characterize the nuclear lamina proteome. To accomplish this, we have leveraged the BioID system, which previously has been successfully used to characterize the nuclear lamina proteome. Second, we have established a system to identify proteins that bind to LADs by developing a chromatin directed BioID system. We combined the BioID system with the m6A-tracer system which binds to LADs in live cells to identify LAD proximal and nuclear lamina proteins. In combining these datasets, we have further characterized the protein network at the nuclear lamina as well as identified putative LAD proximal proteins. Our analysis identifies many heterochromatin related proteins related to H3K9 methylation processes as well as many proteins related to cell cycle regulation identifying important proteins essential for LAD function.
2021-03-09 | PXD012943 | Pride
Project description:In mammals, the emergence of totipotency after fertilization involves extensive rearrangements of the spatial positioning of the genome1,2. However, the contribution of spatial genome organization to the regulation of developmental programs is unclear3. Here we generate high-resolution maps of genomic interactions with the nuclear lamina (a filamentous meshwork that lines the inner nuclear membrane) in mouse pre-implantation embryos. We reveal that nuclear organization is not inherited from the maternal germline but is instead established de novo shortly after fertilization. The two parental genomes establish lamina-associated domains (LADs)4 with different features that converge after the 8-cell stage. We find that the mechanism of LAD establishment is unrelated to DNA replication. Instead, we show that paternal LAD formation in zygotes is prevented by ectopic expression of Kdm5b, which suggests that LAD establishment may be dependent on remodelling of H3K4 methylation. Our data suggest a step-wise assembly model whereby early LAD formation precedes consolidation of topologically associating domains.
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Project description:Autophagy is a catabolic membrane trafficking process involved in degradation of cellular constituents through lysosomes, which maintains cell and tissue homeostasis. While much attention has been focused on autophagic turnover of cytoplasmic materials, little is known regarding the role of autophagy in degrading nuclear components. Here we report that autophagy machinery mediates degradation of nuclear lamina in mammalian cells, a process we term laminophagy. The autophagy protein LC3 is present in the nucleus and directly interacts with the nuclear lamina protein Lamin B1, and associates with lamin-associated domains (LADs) on chromatin. This interaction does not downregulate Lamin B1 during starvation, but mediates nuclear lamina degradation upon tumorigenic insults, such as by oncogenic Ras. Laminophagy is achieved by nucleus-to-cytosol transport that delivers Lamin B1 to lysosome for degradation. Inhibiting autophagy or LC3-Lamin B1 interaction prevents oncogenic Ras-induced Lamin B1 loss and delays oncogene-induced cell cycle arrest. Our study unveils a role of autophagy in degrading nuclear materials, and suggests laminophagy as a guarding mechanism protecting cells from tumorigenesis.
2015-10-08 | GSE63440 | GEO
Project description:Regulation of gene expression is highly conserved between vertebrates, yet the genomic binding patterns of transcription factors are poorly conserved, suggesting that other mechanisms may contribute. The spatial organization of chromosomes in the nucleus is known to affect gene activity, but it is unclear to what extent this organization is conserved in evolution. Genome-wide maps of nuclear lamina (NL) interactions show that human and mouse chromosomes have highly similar folding patterns inside the nucleus. Breaks in synteny are often located at transition points between NL interacting and intra-nuclear regions. Data were compared against data from Peric-Hupkes, Meuleman et al. (Molecular Cell, 2010). LaminB1-chromatin interactions were assayed in human ESCs and human HT1080 cells. LaminA-chromatin interactions were assayed in human HT1080 cells. For the all samples there were 2 biological replicates, that were hybridized in a dye-swap design.
2012-10-10 | E-GEOD-22428 | biostudies-arrayexpress
Project description:Several cellular factors, including the nuclear lamina, regulate chromatin composition and architecture. While the interaction of the viral genome with the nuclear lamina has been studied in the context of EBV lytic reactivation, the role of the nuclear lamina in controlling EBV latency has not been investigated. Here, we report that the nuclear lamina is an essential epigenetic regulator of the EBV episome.
2022-03-18 | GSE198954 | GEO
Project description:Stepwise de novo establishment of inactive X chromosome architecture in early development [Embryo HiC]
| PRJNA849504 | ENA
Project description:X chromosome inactivation (XCI) triggers a drastic reprogramming of gene activities and chromosome architecture. However, how the 3D organization of the inactive X chromosome (Xi) is de novo established in vivo in mammals remains poorly understood. By comprehensive stage- and lineage- specific Hi-C mapping, we identified a unique Xist-separated megadomain structure (X-megadomains) on the Xi in mouse early embryos. X-megadomains emerge in extraembryonic lineages during imprinted XCI, in derived extraembryonic endoderm (XEN) cells, and transiently in the embryonic lineages during random XCI, before Dxz4-delineated megadomains (D-megadomains) occur at later stages in a strain-specific manner. Mechanistically, the emergence of X-megadomain boundary coincides with developmentally regulated enhancer activities and cohesin binding in a regulatory region near Xist (XRR). We pinpointed a subregion XRRa that is critical for the X-megadomain boundary. X-megadomains are impaired when XRRa is removed or cohesin is degraded in XEN cells. Importantly, this is accompanied by ectopic activation of regulatory elements and genes near Xist, suggesting that cohesin loading at regulatory elements promotes X-megadomains and confines local gene activities. Finally, the knockout of XRRa in mouse preimplantation embryos severely impairs the activation of Xist and the initiation of XCI. Hence, our data not only reveal stepwise chromosome folding during de novo XCI in vivo, but also support a model that regulatory element-dependent gene activation and cohesin loading simultaneously promote essential transcription activities and subsequent self-insulation amid global silencing during the early stage of XCI.
2024-09-10 | GSE206158 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE35777: A molecular mechanism for compartmentalization and silencing of chromatin domains at the nuclear lamina [Tiling Array] GSE36048: A molecular mechanism for compartmentalization and silencing of chromatin domains at the nuclear lamina [ChIP-seq] Refer to individual Series
2012-02-24 | E-GEOD-36049 | biostudies-arrayexpress
Project description:A large fraction of the mammalian genome is organized into inactive chromosomal domains associated with the nuclear lamina. Using genomic repositioning assays we show that Lamina associated domains (LADs), spanning the developmentally regulated IgH and Cyp3a loci, contain transportable DNA regions that associate chromatin with the nuclear lamina and repress gene activity in fibroblasts. We characterized DNA regions within LADs that are functionally capable of positioning chromatin domains at the inner nuclear membrane (INM) lamina. We mapped and characterized the IgH and other LADs in murine fibroblasts. We show that these murine LADs have a unique chromatin structure with discrete boundaries. We demonstrate DNA regions within LADs that are capable of directing the association of chromatin domains with the INM-lamina as well as the silencing of a co-integrated reporter gene.
2012-02-24 | E-GEOD-36048 | biostudies-arrayexpress