Stochastic genome-nuclear lamina interactions: Modulating roles of Lamin A and BAF
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE55066 | GEO | 2014/02/15
SECONDARY ACCESSION(S): PRJNA238367
REPOSITORIES: GEO
Similar Datasets
Project description:The nuclear lamina (NL) is a filamentous layer lining the inner-nuclear-membrane (INM) that aids in the organization of the genome in large domains of low transcriptional activity. Recently, it was shown that the single-cell genome-NL interactions are much more dynamic than previously anticipated, which challenges the concept of the NL as a safe guard for transcriptional repressed genes. Here we discuss the role of the NL in light of these new findings and introduce Lamin A and BAF as potential modulators of LAD positioning BAF-chromatin and Lamin B2-chromatin interactions were assayed in human HT1080 by DamID on Nimblegen microarrays, with two biological replicates each, that were hybridized in a dye-swap design.
2014-02-15 | E-GEOD-55066 | biostudies-arrayexpress
Project description:The nuclear lamina (NL) interacts with hundreds of large genomic regions termed lamina-associated domains (LADs). The dynamics of these interactions and the relation to epigenetic modifications are poorly understood. We visualized the fate of LADs in single cells using a novel 'molecular contact memory' approach. In each interphase nucleus, only ~30% of LADs are positioned at the periphery; these LADs are in intermittent molecular contact with the NL but remain constrained to the periphery. Upon mitosis, LAD positioning is not detectably inherited but instead is stochastically reshuffled. Contact of individual LADs with the NL correlates with their degree of H3K9 dimethylation in single cells, and inactivation of the H3K9 methyltransferase G9a reduces the NL contact frequencies. These results indicate that nuclear positioning and histone modification of LADs are both stochastic yet linked in single cells. Collectively, these results highlight principles of the dynamic spatial architecture of chromosomes.
2013-01-31 | GSE40094 | GEO
Project description:The nuclear lamina (NL) interacts with hundreds of large genomic regions termed lamina-associated domains (LADs). The dynamics of these interactions and the relation to epigenetic modifications are poorly understood. We visualized the fate of LADs in single cells using a novel 'molecular contact memory' approach. In each interphase nucleus, only ~30% of LADs are positioned at the periphery; these LADs are in intermittent molecular contact with the NL but remain constrained to the periphery. Upon mitosis, LAD positioning is not detectably inherited but instead is stochastically reshuffled. Contact of individual LADs with the NL correlates with their degree of H3K9 dimethylation in single cells, and inactivation of the H3K9 methyltransferase G9a reduces the NL contact frequencies. These results indicate that nuclear positioning and histone modification of LADs are both stochastic yet linked in single cells. Collectively, these results highlight principles of the dynamic spatial architecture of chromosomes. LaminB1-chromatin interactions were assayed in human HT1080 cells by induction of Dam_LMNB1 expression in a stable cell line with shield1.
2013-01-31 | E-GEOD-40094 | biostudies-arrayexpress
Project description:The nuclear lamina (NL) interacts with hundreds of large genomic regions termed lamina-associated domains (LADs). The dynamics of these interactions and the relation to epigenetic modifications are poorly understood. We visualized the fate of LADs in single cells using a novel 'molecular contact memory' approach. In each interphase nucleus, only ~30% of LADs are positioned at the periphery; these LADs are in intermittent molecular contact with the NL but remain constrained to the periphery. Upon mitosis, LAD positioning is not detectably inherited but instead is stochastically reshuffled. Contact of individual LADs with the NL correlates with their degree of H3K9 dimethylation in single cells, and inactivation of the H3K9 methyltransferase G9a reduces the NL contact frequencies. These results indicate that nuclear positioning and histone modification of LADs are both stochastic yet linked in single cells. Collectively, these results highlight principles of the dynamic spatial architecture of chromosomes.
2013-01-31 | GSE40111 | GEO
Project description:The nuclear lamina (NL) interacts with hundreds of large genomic regions termed lamina-associated domains (LADs). The dynamics of these interactions and the relation to epigenetic modifications are poorly understood. We visualized the fate of LADs in single cells using a novel 'molecular contact memory' approach. In each interphase nucleus, only ~30% of LADs are positioned at the periphery; these LADs are in intermittent molecular contact with the NL but remain constrained to the periphery. Upon mitosis, LAD positioning is not detectably inherited but instead is stochastically reshuffled. Contact of individual LADs with the NL correlates with their degree of H3K9 dimethylation in single cells, and inactivation of the H3K9 methyltransferase G9a reduces the NL contact frequencies. These results indicate that nuclear positioning and histone modification of LADs are both stochastic yet linked in single cells. Collectively, these results highlight principles of the dynamic spatial architecture of chromosomes. 12 RNA-seq experiments for 6 samples, each with a biological replicate: m6ATracer-VP16+/DamLaminB1+ m6ATracer-VP16+/DamLaminB1- m6ATracer-VP16-/DamLaminB1- m6ATracer-GFP+/DamLaminB1+ m6ATracer-GFP+/DamLaminB1- m6ATracer-GFP-/DamLaminB1-
2013-01-31 | E-GEOD-40111 | biostudies-arrayexpress
Project description:Mammalian genomes contain hundreds of lamina-associated domains (LADs), which are large, often megabase-sized heterochromatin domains that are anchored to the nuclear lamina (NL). Even though LADs play a key role in the spatial organization of the genome and potently repress gene activity, it is not yet understood how their interactions with the NL are encoded in their DNA. Here, we investigated the principles that govern LAD-NL interactions by taking a "LAD scrambling" approach. This approach relies on 1) local "hopping" of a Sleeping Beauty transposon to randomly insert loxP sites within and around a LAD of choice; and 2) Cre-mediated recombination between the loxP sites. This approach is highly efficient, enabling us to establish a large collection of clonal cell lines with deletions and inversions up to ~2Mb in size, spanning LAD and their flanking inter-LAD sequences. Mapping of NL interactions in these clones revealed that a single LAD contacts the NL through multiple regions. These regions act cooperatively and redundantly; however, some have more affinity for the NL and can boost NL contacts of neighbouring sequences. We also observed a crosstalk between two neighbouring LADs, when close enough to each other. Finally, changes in the heterochromatin mark H3K9me3 only partially mirrored changes in NL contacts. They also correlated more with gene expression changes than NL contacts did. These principles of LAD - NL interactions provide insight into the overall architecture of the genome and the impact on gene regulation.
2023-12-19 | GSE250306 | GEO
Project description:Mammalian genomes contain hundreds of lamina-associated domains (LADs), which are large, often megabase-sized heterochromatin domains that are anchored to the nuclear lamina (NL). Even though LADs play a key role in the spatial organization of the genome and potently repress gene activity, it is not yet understood how their interactions with the NL are encoded in their DNA. Here, we investigated the principles that govern LAD-NL interactions by taking a "LAD scrambling" approach. This approach relies on 1) local "hopping" of a Sleeping Beauty transposon to randomly insert loxP sites within and around a LAD of choice; and 2) Cre-mediated recombination between the loxP sites. This approach is highly efficient, enabling us to establish a large collection of clonal cell lines with deletions and inversions up to ~2Mb in size, spanning LAD and their flanking inter-LAD sequences. Mapping of NL interactions in these clones revealed that a single LAD contacts the NL through multiple regions. These regions act cooperatively and redundantly; however, some have more affinity for the NL and can boost NL contacts of neighbouring sequences. We also observed a crosstalk between two neighbouring LADs, when close enough to each other. Finally, changes in the heterochromatin mark H3K9me3 only partially mirrored changes in NL contacts. They also correlated more with gene expression changes than NL contacts did. These principles of LAD - NL interactions provide insight into the overall architecture of the genome and the impact on gene regulation.
2023-12-19 | GSE250085 | GEO
Project description:The nuclear lamina (NL) is thought to aid in the spatial organization of interphase chromosomes by providing an anchoring platform for hundreds of large genomic regions named lamina associated domains (LADs). Recently, a new live-cell imaging approach demonstrated directly that LAD-NL interactions are dynamic and in part stochastic. Here we discuss implications of these new findings and introduce Lamin A and BAF as potential modulators of stochastic LAD positioning.
| S-EPMC4049918 | biostudies-literature
Project description:Processes shaping the 3-dimensional (3D) human genome remain elusive. We present Chrom3D, a user-friendly 3D whole-genome modeling software that dynamically simulates the radial positioning of topological domains (TADs) in the nucleus. We integrate Hi-C and lamin-associated domain (LAD) information to generate high-resolution ensembles of models that recapitulate single-cell TAD distribution. Chrom3D reveals dynamic TADs and TADs constitutively placed at the nuclear periphery or nuclear interior. TAD stability in these compartments is consistent with differences in TAD gene density and expression level. A- and B-type lamins as radial constraints differentially skew LAD distribution towards the nuclear interior or periphery. Predictions of radial LAD placement in model ensembles are validated by quantitative imaging. Chrom3D models reveal unexpected features of LAD regulation in the nuclear interior in cells from laminopathy patients with a LMNA mutation. Integration of radial positioning constraints in 3D genome models enables the study spatial gene regulation in disease contexts.
2016-12-22 | GSE81671 | GEO
Project description:Specific interactions of the genome with the nuclear lamina (NL) are thought to assist chromosome folding inside the nucleus and to contribute to the regulation of gene expression. High-resolution mapping has recently identified hundreds of large, sharply defined lamina-associated domains (LADs) in the human genome, and suggested that the insulator protein CTCF may help to demarcate these domains. Here, we report the detailed structure of LADs in Drosophila cells, and investigate the putative roles of five insulator proteins in LAD organization. We found that of these five proteins, only SU(HW) binds preferentially at LAD borders and at specific positions inside LADs, while GAF, CTCF, BEAF-32 and DWG are mostly absent from these regions. By knockdown and overexpression studies we demonstrate that SU(HW) weakens LAD – NL interactions by a local antagonistic effect. Our results provide insights into the evolution of LAD organization and reveal a role for SU(HW) in the regulation of genome – NL interactions.
2011-01-24 | GSE20312 | GEO