Similar Datasets
Project description:In this study, we profiled genome-Nuclear Lamina (NL) contacts during the first stages of mouse embryonic development. We discovered a remarkable cell-to-cell variability in NL-contacts at the 2-cell stage, which is particularly strong on the paternal allele. We additionally obtained single-cell profiles for H3K27me3, H3K9me3 and DNA accessibility at this stage, but did not observe the same large-scale variability. The variability in NL-contacts did not appear to affect the transcription of underlying genes. Comparing NL-contact profiles with diverse histone modification profiles showed that large regions of typical NL-contacts are lost and instead are enriched for H3K27me3 during early development. To investigate the relationship between H3K27me3 and NL association, we used a conditional EED KO mouse model, which results in an absence of H3K27me3 during oocyte development and the early embryo. Profiling NL-contacts at the 2-cell stage in this system revealed that regions enriched with H3K27me3 in WT regain NL association in the EED maternal KO. In addition, the loss of H3K27me3 resulted in more similar NL association profiles on the maternal and paternal allele. Together, these results suggest that H3K27me3 antagonizes NL association and that the non-canonical broad H3K27me3 domains present in the early embryo may be responsible for the early-embryo specific loss of NL associations in these regions.
2024-08-09 | GSE217462 | GEO
Project description:In this study, we profiled genome-Nuclear Lamina (NL) contacts during the first stages of mouse embryonic development. We discovered a remarkable cell-to-cell variability in NL-contacts at the 2-cell stage, which is particularly strong on the paternal allele. We additionally obtained single-cell profiles for H3K27me3, H3K9me3 and DNA accessibility at this stage, but did not observe the same large-scale variability. The variability in NL-contacts did not appear to affect the trascription of underlying genes. Comparing NL-contact profiles with diverse histone modification profiles showed that large regions of typical NL-contacts are lost and instead are inriched for H3K27me3 during early development. To investigate the relationship between H3K27me3 and NL association, we used a conditional EED KO mouse model, which results in an absence of H3K27me3 during oocyte development and the early embryo. Profiling NL-contacts at the 2-cell stage in this syste revealed that regions enriched with H3K27me3 in WT regain NL association in the EED maternal KO. In addition, the loss of H3K27me3 resulted in more similar NL association profiles on the maternal and paternal allele. Together, these results suggest that H3K27me3 antagonizes NL association and that the non-canonical broad H3K27me3 domains present in the early embryo may be responsible for the early-embryo specific loss of NL associations in these regions.
2024-08-09 | GSE273151 | GEO
Project description:In this study, we profiled genome-Nuclear Lamina (NL) contacts during the first stages of mouse embryonic development. We discovered a remarkable cell-to-cell variability in NL-contacts at the 2-cell stage, which is particularly strong on the paternal allele. We additionally obtained single-cell profiles for H3K27me3, H3K9me3 and DNA accessibility at this stage, but did not observe the same large-scale variability. The variability in NL-contacts did not appear to affect the transcription of underlying genes. Comparing NL-contact profiles with diverse histone modification profiles showed that large regions of typical NL-contacts are lost and instead are enriched for H3K27me3 during early development. To investigate the relationship between H3K27me3 and NL association, we used a conditional EED KO mouse model, which results in an absence of H3K27me3 during oocyte development and the early embryo. Profiling NL-contacts at the 2-cell stage in this system revealed that regions enriched with H3K27me3 in WT regain NL association in the EED maternal KO. In addition, the loss of H3K27me3 resulted in more similar NL association profiles on the maternal and paternal allele. Together, these results suggest that H3K27me3 antagonizes NL association and that the non-canonical broad H3K27me3 domains present in the early embryo may be responsible for the early-embryo specific loss of NL associations in these regions.
2024-08-09 | GSE218597 | GEO
Project description:How the nuclear lamina (NL) impacts on global chromatin architecture is poorly understood. Here, we show that NL disruption in Drosophila S2 cells leads to chromatin compaction and repositioning from the nuclear envelope. This increases the chromatin density in a fraction of topologically-associating domains (TADs) enriched in active chromatin and enhances interactions between active and inactive chromatin. Importantly, upon NL disruption the NL-associated TADs become more acetylated at histone H3 and less compact, while background transcription is derepressed. Two-colour FISH confirms that a TAD becomes less compact following its release from the NL. Finally, polymer simulations show that chromatin binding to the NL can per se compact attached TADs. Collectively, our findings demonstrate a dual function of the NL in shaping the 3D genome. Attachment of TADs to the NL makes them more condensed but decreases the overall chromatin density in the nucleus by stretching interphase chromosomes.
| S-EPMC6414625 | biostudies-literature
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.
| S-EPMC6546605 | biostudies-literature
Project description:Nonrandom chromosomal conformations, including promoter-enhancer loopings that bypass kilobases or megabases of linear genome, provide a crucial layer of transcriptional regulation and move vast amounts of non-coding sequence into the physical proximity of genes that are important for neurodevelopment, cognition and behaviour. Activity-regulated changes in the neuronal '3D genome' could govern transcriptional mechanisms associated with learning and plasticity, and loop-bound intergenic and intronic non-coding sequences have been implicated in psychiatric and adult-onset neurodegenerative disease. Recent studies have begun to clarify the roles of spatial genome organization in normal and abnormal cognition.
| S-EPMC5503467 | biostudies-literature
Project description:The genome can be divided into two spatially segregated compartments, A and B, which partition active and inactive chromatin states. While constitutive heterochromatin is predominantly located within the B compartment near the nuclear lamina, facultative heterochromatin marked by H3K27me3 spans both compartments. How epigenetic modifications, compartmentalization, and lamina association collectively maintain heterochromatin architecture remains unclear. Here we develop Lamina-Inducible Methylation and Hi-C (LIMe-Hi-C) to jointly measure chromosome conformation, DNA methylation, and lamina positioning. Through LIMe-Hi-C, we identify topologically distinct sub-compartments with high levels of H3K27me3 and differing degrees of lamina association. Inhibition of Polycomb repressive complex 2 (PRC2) reveals that H3K27me3 is essential for sub-compartment segregation. Unexpectedly, PRC2 inhibition promotes lamina association and constitutive heterochromatin spreading into H3K27me3-marked B sub-compartment regions. Consistent with this repositioning, genes originally marked with H3K27me3 in the B compartment, but not the A compartment, remain largely repressed, suggesting that constitutive heterochromatin spreading can compensate for H3K27me3 loss at a transcriptional level. These findings demonstrate that Polycomb sub-compartments and their antagonism with lamina association are fundamental features of genome structure. More broadly, by jointly measuring nuclear position and Hi-C contacts, our study demonstrates how compartmentalization and lamina association represent distinct but interdependent modes of heterochromatin regulation.
| S-EPMC9300685 | biostudies-literature
Project description:In bacterial genomes, the compactly encoded genes and operons are well organized, with genes in the same biological pathway or operons in the same regulon close to each other on the genome sequence. In addition, the linearly close genes have a higher probability of co-expression and their protein products tend to form protein-protein interactions. However, the organization features of bacterial genomes in a three-dimensional space remain elusive. The DNA interaction data of Escherichia coli, measured by the genome conformation capture (GCC) technique, have recently become available, which allowed us to investigate the spatial features of bacterial genome organization.By renormalizing the GCC data, we compared the interaction frequency of operon pairs in the same regulon with that of random operon pairs. The results showed that arrangements of operons in the E. coli genome tend to minimize the spatial distance between operons in the same regulon. A similar global organization feature exists for genes in biological pathways of E. coli. In addition, the genes close to each other spatially (even if they are far from each other on the genome sequence) tend to be co-expressed and form protein-protein interactions. These results provided new insights into the organization principles of bacterial genomes and support the notion of transcription factory.This study revealed the organization features of Escherichia coli genomic functional units in the 3D space and furthered our understanding of the link between the three-dimensional structure of chromosomes and biological function.
| S-EPMC4326437 | biostudies-literature
Project description:The nuclear lamina is an intermediate filament meshwork adjacent to the inner nuclear membrane (INM) that plays a critical role in maintaining nuclear shape and regulating gene expression through chromatin interactions. Studies have demonstrated that A- and B-type lamins, the filamentous proteins that make up the nuclear lamina, form independent but interacting networks. However, whether these lamin subtypes exhibit a distinct spatial organization or whether their organization has any functional consequences is unknown. Using stochastic optical reconstruction microscopy (STORM) our studies reveal that lamin B1 and lamin A/C form concentric but overlapping networks, with lamin B1 forming the outer concentric ring located adjacent to the INM. The more peripheral localization of lamin B1 is mediated by its carboxyl-terminal farnesyl group. Lamin B1 localization is also curvature- and strain-dependent, while the localization of lamin A/C is not. We also show that lamin B1's outer-facing localization stabilizes nuclear shape by restraining outward protrusions of the lamin A/C network. These two findings, that lamin B1 forms an outer concentric ring and that its localization is energy-dependent, are significant as they suggest a distinct model for the nuclear lamina-one that is able to predict its behavior and clarifies the distinct roles of individual nuclear lamin proteins and the consequences of their perturbation.
| S-EPMC6410836 | biostudies-literature
Project description:The nuclear lamina (NL) is a meshwork of lamins and lamin-associated proteins lining the nuclear envelope (NE). Chromatin adjoining the NL in lamina-associated domains (LADs) is densely packed and contains predominantly silent genes. However, how the NL impacts on global chromatin architecture is poorly understood. Here, we show that NL disruption in Drosophila S2 cells leads to bulk chromatin compactization and repositioning from the NE. This increases the chromatin density in the topologically-associating domains (TADs) harboring active genes, and enhances inter-TAD interactions resulting in the intermingling of active and inactive compartments. Importantly, upon NL disruption, a fraction of TADs strongly overlapping with LADs becomes less compact, whilst resident genes are derepressed. Two-color FISH confirms that a a TAD is more decompacted following its release from the NL. Finally, polymer simulations show that chromatin binding to the NL can per se compact attached TADs. Collectively, our findings demonstrate a dual function of the NL in shaping the 3D genome. Attachment of TADs to the NL makes them more condensed but decreases the overall chromatin density in the nucleus by stretching interphase chromosomes.
2019-02-08 | GSE110082 | GEO