Ontology highlight
ABSTRACT:
PROVIDER: PRJNA256472 | ENA |
REPOSITORIES: ENA
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Project description:Wash regulates lamin-dependent nuclear genome organization [DamID]
| PRJNA256473 | ENA
Project description:Wash regulates lamin-dependent nuclear genome organization [Chromatin Accessibility]
| PRJNA256474 | ENA
Project description:The cytoplasmic functions of Wiskott-Aldrich Syndrome family (WASP) proteins are well known and include roles in cytoskeleton reorganization and membrane-cytoskeletal interactions important for membrane/vesicle trafficking, morphogenesis, immune response and signal transduction. Mis-regulation of these proteins is associated with immune deficiency and metastasis. Cytoplasmic WASP proteins act as effectors of Rho family GTPases and polymerize branched actin through the Arp2/3 complex. However, recent evidence has revealed that this classically cytoplasmic protein family also functions in the nucleus. Previously, we identified Drosophila washout (wash) as a new member of the WASP family with essential cytoplasmic roles in early development. Here we show that Wash is also present in the nucleus and plays a key role in nuclear organization via its interaction with Lamin Dm0 at the nuclear envelope. Wash and Lamin Dm0 occupy similar genomic regions that overlap with transcriptionally silent chromatin including constitutive heterochromatin. Strikingly, wash mutant and knockdown nuclei exhibit the same abnormal wrinkled morphology observed in diverse laminopathies, including the Hutchinson-Gilford progeria syndrome, and consistent with disruption of the nuclear organization of several sub-nuclear structures including cajal bodies and the chromocenter in salivary glands. We also found that Wash and Lamin knockdown disrupt chromatin accessibility of repressive compartments in agreement with an observed global redistribution of repressive histone modifications. Functional genetic approaches show wash mutants exhibit similar phenotypes to lamin Dm0 mutants, suggesting they participate in similar regulatory networks. Our results reveal a novel role for Wash in modulating nuclear organization via its interaction with the nuclear envelope protein Lamin Dm0. These findings highlight the functional complexity of WASP family proteins and provide new venues to understand their molecular roles in cell biology and disease. DamID chromatin profiling demostrate that Wash binds similar regions to those bound by Lamin Dm0, in particular transcriptional silent chromatin
2015-03-10 | GSE59853 | GEO
Project description:The cytoplasmic functions of Wiskott-Aldrich Syndrome family (WASP) proteins are well known and include roles in cytoskeleton reorganization and membrane-cytoskeletal interactions important for membrane/vesicle trafficking, morphogenesis, immune response and signal transduction. Mis-regulation of these proteins is associated with immune deficiency and metastasis. Cytoplasmic WASP proteins act as effectors of Rho family GTPases and polymerize branched actin through the Arp2/3 complex. However, recent evidence has revealed that this classically cytoplasmic protein family also functions in the nucleus. Previously, we identified Drosophila washout (wash) as a new member of the WASP family with essential cytoplasmic roles in early development. Here we show that Wash is also present in the nucleus and plays a key role in nuclear organization via its interaction with Lamin Dm0 at the nuclear envelope. Wash and Lamin Dm0 occupy similar genomic regions that overlap with transcriptionally silent chromatin including constitutive heterochromatin. Strikingly, wash mutant and knockdown nuclei exhibit the same abnormal wrinkled morphology observed in diverse laminopathies, including the Hutchinson-Gilford progeria syndrome, and consistent with disruption of the nuclear organization of several sub-nuclear structures including cajal bodies and the chromocenter in salivary glands. We also found that Wash and Lamin knockdown disrupt chromatin accessibility of repressive compartments in agreement with an observed global redistribution of repressive histone modifications. Functional genetic approaches show wash mutants exhibit similar phenotypes to lamin Dm0 mutants, suggesting they participate in similar regulatory networks. Our results reveal a novel role for Wash in modulating nuclear organization via its interaction with the nuclear envelope protein Lamin Dm0. These findings highlight the functional complexity of WASP family proteins and provide new venues to understand their molecular roles in cell biology and disease. We evaluated the effect of Wash knockdown in S2R+ cells on chromatin accessibility using an M.SssI-based approach.
2015-03-10 | GSE59852 | GEO
Project description:Drosophila Haspin kinase phosphorylates Histone H3 at threonine 3 at centromeric heterochromatin and either lamin- or polycomb-enriched euchromatic regions, being required for nuclear organization of interphase cells and polycomb-dependent gene silencing.
2020-08-07 | GSE98223 | GEO
Project description:As we age, structural changes contribute to progressive decline in organ function, which in the heart acts through poorly characterized mechanisms. Utilizing the rapidly aging fruit fly model with its significant homology to the human cardiac proteome, we found that cardiomyocytes exhibit progressive loss of Lamin C (mammalian Lamin A/C homologue) with age. Unlike other tissues and laminopathies, we observe decreasing nuclear size, while nuclear stiffness increases. Premature genetic reduction of Lamin C phenocopies aging’s effects on the nucleus, and subsequently decreases heart contractility and sarcomere organization. Surprisingly, Lamin C reduction downregulates myogenic transcription factors and cytoskeletal regulators, possibly via reduced chromatin accessibility. Subsequently, we find an adult-specific role for cardiac transcription factors and show that maintenance of Lamin C sustains their expression and prevents age-dependent cardiac decline. Our findings are conserved in aged non-human primates and mice, demonstrating age-dependent nuclear remodeling is a major mechanism contributing to cardiac dysfunction.
2022-11-01 | GSE185923 | GEO
Project description:Lamin A/C, a critical nuclear lamina protein, is essential for maintaining nuclear architecture, organizing chromatin and preserving genomic stability. However, its role in directly regulating DNA replication remains unclear. This study investigates how Lamin A/C orchestrates replication initiation by modulating chromatin structure and interacting with proliferating cell nuclear antigen (PCNA). Utilizing high-resolution imaging, chromatin accessibility assays, and sequencing, we demonstrate that Lamin A/C stabilizes replication domains (RDs) by restricting chromatin mobility, preserving spatial organization, and maintaining accessibility. Furthermore, Lamin A/C interacts with PCNA via its Ig-fold domain, regulating PCNA availability by sequestering a pool of PCNA and modulating its expression, and thereby controlling its recruitment to replication machinery. The loss of Lamin A/C results in chromatin architecture reorganization and elevated PCNA availability at RDs, which coordinately trigger excessive activation of replication origins, leading to replication stress and DNA damage. These disruptions prolong the S phase and compromise genome stability, highlighting Lamin A/C as a critical gatekeeper of balanced replication initiation. Our findings reveal Lamin A/C’s dual role in chromatin organization and replication machinery regulation, offering valuable insights into its involvement in replication-associated diseases such as cancer and viral infections and highlighting potential therapeutic opportunities through targeting replication dynamics.
2025-02-22 | GSE289475 | GEO
Project description:Lamin A/C, a critical nuclear lamina protein, is essential for maintaining nuclear architecture, organizing chromatin and preserving genomic stability. However, its role in directly regulating DNA replication remains unclear. This study investigates how Lamin A/C orchestrates replication initiation by modulating chromatin structure and interacting with proliferating cell nuclear antigen (PCNA). Utilizing high-resolution imaging, chromatin accessibility assays, and sequencing, we demonstrate that Lamin A/C stabilizes replication domains (RDs) by restricting chromatin mobility, preserving spatial organization, and maintaining accessibility. Furthermore, Lamin A/C interacts with PCNA via its Ig-fold domain, regulating PCNA availability by sequestering a pool of PCNA and modulating its expression, and thereby controlling its recruitment to replication machinery. The loss of Lamin A/C results in chromatin architecture reorganization and elevated PCNA availability at RDs, which coordinately trigger excessive activation of replication origins, leading to replication stress and DNA damage. These disruptions prolong the S phase and compromise genome stability, highlighting Lamin A/C as a critical gatekeeper of balanced replication initiation. Our findings reveal Lamin A/C’s dual role in chromatin organization and replication machinery regulation, offering valuable insights into its involvement in replication-associated diseases such as cancer and viral infections and highlighting potential therapeutic opportunities through targeting replication dynamics.
2025-02-22 | GSE289473 | GEO
Project description:Organization of the genome into compacted chromatin is a eukaryotic innovation facilitating increased sophistication in transcriptional regulation. In metazoa coiled-coil lamin proteins are major components of the chromatin organizer at the nuclear periphery and maintain nuclear integrity. While identifiable lamin homologues are restricted to metazoans, morphologically analogous structures maintaining nuclear organization in other eukaryotic lineages are known, but the molecular constituents remain undefined. Trypanosoma brucei NUP-1 is a large coiled-coil protein associated with fibrils at the inner face of the nuclear envelope. Using transcriptome analysis in combination with RNA interference and various imaging techniques, we demonstrate that NUP-1 forms a stable immobile cage around the nucleus, is required for viability and nuclear structural integrity, directs the positional organization of nuclear pore complexes, and serves to organize chromatin and specifically repress genes located at the nuclear periphery involved in immune evasion. Based on architectural similarity and functionality, we propose that NUP-1 is a novel, highly divergent lamin The effect of Nup-1 depletion on the transcriptome was examined in three independent experiments (A, B, & C). T. brucei cultures were either treated with RNAi (plus) or left untreated (minus) and RNA was extracted from each sample at the indicated time point (0h, 6h, 12h, 24h, or 48h). Two color microarrays were performed comparing treated and untreated samples at each time point. Dye swaps were performed and are indicated. Replicates of t=12h and t=24h for sample B were also included.
2011-12-15 | E-GEOD-26256 | biostudies-arrayexpress
Project description:Organization of the genome into compacted chromatin is a eukaryotic innovation facilitating increased sophistication in transcriptional regulation. In metazoa coiled-coil lamin proteins are major components of the chromatin organizer at the nuclear periphery and maintain nuclear integrity. While identifiable lamin homologues are restricted to metazoans, morphologically analogous structures maintaining nuclear organization in other eukaryotic lineages are known, but the molecular constituents remain undefined. Trypanosoma brucei NUP-1 is a large coiled-coil protein associated with fibrils at the inner face of the nuclear envelope. Using transcriptome analysis in combination with RNA interference and various imaging techniques, we demonstrate that NUP-1 forms a stable immobile cage around the nucleus, is required for viability and nuclear structural integrity, directs the positional organization of nuclear pore complexes, and serves to organize chromatin and specifically repress genes located at the nuclear periphery involved in immune evasion. Based on architectural similarity and functionality, we propose that NUP-1 is a novel, highly divergent lamin
2011-12-15 | GSE26256 | GEO