Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA108853 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE10697: Self-Self Hybridisation were used to set confidence 99% intervals GSE10698: The effects of artificial tethering of chromosomes to the nuclear periphery using LacI/lap2b anchorage constructs 1 GSE10699: The effects of artificial tethering of chromosomes to the nuclear periphery using LacI/lap2b anchorage constructs 2 Background: The spatial organisation of the genome in the nucleus has a role in the regulation of gene expression. In mammals, chromosomal regions with low gene-density are located close to the nuclear periphery. Correlations have also been made between the transcriptional state of some genes and their location near the nuclear periphery. However, a crucial issue is whether this level of nuclear organisation directly affects gene function, rather than merely reflecting it. Methodology: To directly investigate whether proximity to the nuclear periphery can influence gene expression in mammalian cells. here we relocate specific human chromosomes to the nuclear periphery by tethering them to a protein of the inner nuclear membrane. Principal findings: We show that this can reversibly suppress the expression of some endogenous human genes located near the tethering sites, and even genes further away. However, the expression of many other genes is not detectably reduced and we show that location at the nuclear periphery is not incompatible with active transcription. The dampening of gene expression around the nuclear periphery is dependent on the activity of histone deacetylases. Significance: Our data show that the radial position within the nucleus can influence the expression of some, but not all, genes. This is compatible with the suggestion that re-localisation of genes to the peripheral zone of the nucleus could be used by metazoans to modulate the expression of selected genes during development and differentiation. Keywords: SuperSeries Refer to individual Series
2010-05-26 | E-GEOD-10701 | biostudies-arrayexpress
Project description:The effects of artificial tethering of chromosomes to the nuclear periphery using LacI/lap2b anchorage constructs, part 1
| PRJNA108851 | ENA
Project description:Background: The spatial organisation of the genome in the nucleus has a role in the regulation of gene expression. In mammals, chromosomal regions with low gene-density are located close to the nuclear periphery. Correlations have also been made between the transcriptional state of some genes and their location near the nuclear periphery. However, a crucial issue is whether this level of nuclear organisation directly affects gene function, rather than merely reflecting it. Methodology: To directly investigate whether proximity to the nuclear periphery can influence gene expression in mammalian cells. here we relocate specific human chromosomes to the nuclear periphery by tethering them to a protein of the inner nuclear membrane. Principal findings: We show that this can reversibly suppress the expression of some endogenous human genes located near the tethering sites, and even genes further away. However, the expression of many other genes is not detectably reduced and we show that location at the nuclear periphery is not incompatible with active transcription. The dampening of gene expression around the nuclear periphery is dependent on the activity of histone deacetylases. Significance: Our data show that the radial position within the nucleus can influence the expression of some, but not all, genes. This is compatible with the suggestion that re-localisation of genes to the peripheral zone of the nucleus could be used by metazoans to modulate the expression of selected genes during development and differentiation. This SuperSeries is composed of the SubSeries listed below.
2008-03-04 | GSE10701 | 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:Nuclear compartmentalization appears to play an important role in regulating metazoan genes. While studies on immunoglobulin (Ig) and other loci have correlated positioning at the nuclear lamina with gene repression, the functional consequences of this compartmentalization remain untested. We devised an approach for inducible tethering of genes to the inner nuclear membrane (INM) and demonstrate with 3D DNA-ImmunoFISH, repositioning of chromosomal regions to the nuclear lamina. Relocalization requires mitotic nuclear envelope breakdown and reformation. Tethering leads to the accumulation of lamin and INM proteins but not to association with pericentromeric heterochromatin or nuclear pore complexes. Recruitment of genes to the INM can result in their transcriptional repression. Using DamID we show that as is the case for our model system, inactive Ig loci at the nuclear periphery are contacted by INM and lamina components. We propose that such molecular interactions are used to compartmentalize and limit the accessibility of Ig loci. Experiment Overall Design: We used microarray to analyze the transcription status of genomic regions are inducibly tethered to the INM
2008-06-11 | E-GEOD-10176 | biostudies-arrayexpress
Project description:Transcriptionally silent heterochromatin preferentially localizes at the nuclear periphery, but, despite this, certain budding yeast genes relocate to the nuclear periphery following gene activation, implicating the nuclear envelope in both transcriptional activation and silencing. It is unclear how these distinct chromatin domains are established, maintained and distinguished from one another at the nuclear envelope. Here we report that nuclear pore complexes (NPCs) facilitate the transition between chromatin states by providing a platform to which chromatin-remodeling and chromatin-modifying complexes bind. In particular, we show that the RSC chromatin-remodeling complex associates with NPCs and that the nucleoporin Nup170p nucleates heterochromatin formation at telomeres through recruitment of Sir4p. Deletion of NUP170 altered subtelomeric chromatin structure, reduced SIR complex binding at telomeres, impaired telomeric silencing and abated telomere tethering. These results support a model in which telomeric heterochromatin formation occurs through telomere-NPC interactions that both promote Sir4p binding at telomeres and permit chromatin-remodeling complexes to mediate the transition between chromatin states. Examination of genome-wide nucleosome positions in WT and nup170∆ cells via next-generation sequencing of mononucleosomal DNA.
2013-02-28 | E-GEOD-36792 | biostudies-arrayexpress
Project description:Nuclear compartmentalization appears to play an important role in regulating metazoan genes. While studies on immunoglobulin (Ig) and other loci have correlated positioning at the nuclear lamina with gene repression, the functional consequences of this compartmentalization remain untested. We devised an approach for inducible tethering of genes to the inner nuclear membrane (INM) and demonstrate with 3D DNA-ImmunoFISH, repositioning of chromosomal regions to the nuclear lamina. Relocalization requires mitotic nuclear envelope breakdown and reformation. Tethering leads to the accumulation of lamin and INM proteins but not to association with pericentromeric heterochromatin or nuclear pore complexes. Recruitment of genes to the INM can result in their transcriptional repression. Using DamID we show that as is the case for our model system, inactive Ig loci at the nuclear periphery are contacted by INM and lamina components. We propose that such molecular interactions are used to compartmentalize and limit the accessibility of Ig loci. Keywords: Inducible
2008-01-16 | GSE10176 | GEO
Project description:Cell cycle progression into mitosis induce cellular rearrangements such as mitotic spindle formation, Golgi fragmentation, and nuclear envelope breakdown. Like certain retroviruses, nuclear delivery of HPV16 genomes is facilitated by these processes during entry into host cells by tethering of the viral DNA to mitotic chromosomes through the minor capsid protein L2. However, the mechanism of delivery onto and tethering to the condensed chromosomes is barely understood on a mechanistic level. To date it is unclear, which cellular proteins facilitate this process in interaction with L2 or how this process is regulated. Here, we discovered that HPV16 minor capsid protein L2 is phosphorylated during entry upon mitosis onset on conserved residues within the chromosome-binding region (CBR) that is responsible for nuclear import. The crucial L2 phosphorylations occurred sequentially by the master mitotic kinases CDK1 and PLK1. L2 phosphorylation, thus, not only regulated timely delivery of HPV16 vDNA to mitotic chromatin at mitosis onset, but also likely resulted in a conformational switch in L2 that allowed engagement of cellular proteins for this purpose. In summary, our work demonstrates for the first time a crucial role of mitotic kinases for nuclear entry of a DNA virus and provides important insights into the molecular mechanism of pathogen import into the nucleus during mitosis.
2022-12-22 | PXD028704 | Pride
Project description:Transcriptionally silent heterochromatin preferentially localizes at the nuclear periphery, but, despite this, certain budding yeast genes relocate to the nuclear periphery following gene activation, implicating the nuclear envelope in both transcriptional activation and silencing. It is unclear how these distinct chromatin domains are established, maintained and distinguished from one another at the nuclear envelope. Here we report that nuclear pore complexes (NPCs) facilitate the transition between chromatin states by providing a platform to which chromatin-remodeling and chromatin-modifying complexes bind. In particular, we show that the RSC chromatin-remodeling complex associates with NPCs and that the nucleoporin Nup170p nucleates heterochromatin formation at telomeres through recruitment of Sir4p. Deletion of NUP170 altered subtelomeric chromatin structure, reduced SIR complex binding at telomeres, impaired telomeric silencing and abated telomere tethering. These results support a model in which telomeric heterochromatin formation occurs through telomere-NPC interactions that both promote Sir4p binding at telomeres and permit chromatin-remodeling complexes to mediate the transition between chromatin states.
2013-02-28 | GSE36792 | GEO