Transcriptome of LBR-null mouse kidneys
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE169240 | GEO | 2021/06/01
REPOSITORIES: GEO
Similar Datasets
Project description:Transcriptome of LBR-null mouse kidneys
| PRJNA715765 | ENA
Project description:Emerin and LBR are abundant transmembrane proteins of the nuclear envelope (NE) that are concentrated at the inner nuclear membrane (INM). Although both proteins interact with chromatin and nuclear lamins, they have distinctive biochemical and functional properties. Here we have deployed proximity labeling using the engineered biotin ligase TurboID (TbID) and quantitative proteomics to compare the neighborhoods of emerin and LBR in cultured mouse embryonic fibroblasts (MEFs). Our analysis revealed 232 high confidence proximity partners (HCPP) that interact selectively with emerin and/or LBR, 49 of which are shared by both. These included previously characterized NE-concentrated proteins, as well as a host of additional proteins not previously linked to emerin or LBR functions. Many of these are TM proteins of the ER and include two E3 ubiquitin ligases. Using the proximity ligation assay as an orthogonal approach, we validated the interactions described by proximity labeling for 11/13 proteins analyzed, supporting the robustness of our analysis. Overall, this work presents methodology that may be used for large-scale mapping of the landscape of the INM and reveals a group of new proteins with potential functional connections to emerin and LBR.
2022-05-02 | MSV000089356 | MassIVE
Project description:Two proteins have previously been shown to be necessary and sufficient to tether heterochromatin at the nuclear envelope. The lamin B receptor (Lbr) is expressed during development, but downregulates upon rod differentiation. A second tether is the intermediate filament lamin A (LA), which is not normally expressed in murine rods.To determine how heterochromatin tethering affects the genome, we used in vivo electroporation to misexpress LA or Lbr in mature rods in the absence of degeneration, resulting in the restoration of conventional nuclear architecture. Using scRNA-seq, we show that reorganizing the nucleus via LA/Lbr misexpression has only minor effects on rod gene expression. Next, using ATAC-seq, we show that LA and Lbr similarly increase genome accessibility. Novel ATAC-seq peaks tended to distal to genes, but some peaks were associated with stress-responsive genes. Together, our data reveal that heterochromatin tethers have a global effect on genome accessibility, and suggest that LA –dependent genome reconfiguration might contribute to the stress response of rod photoreceptors.
2023-10-12 | GSE240465 | GEO
Project description:To probe the functional consequences of nuclear lamina genome association, we made LMNA, LBR, and double LMNA/LBR K562 knockout lines. We first examined the genome interaction changes with nulcear lamina using LMNB1 DamID seq and further assessed the functional consequences of these changes using RNA-seq and repli-seq.
2024-04-04 | GSE263012 | GEO
Project description:Neurodegenerative diseases are accompanied by dynamic changes in gene expression, including the upregulation of hallmark stress-responsive genes. While the transcriptional pathways that impart adaptive and maladaptive gene expression signatures have been the focus of intense study, the role of higher order nuclear organization in this process is less clear. Here, we examine the role of the nuclear lamina in genome organization during the degeneration of rod photoreceptors. Two proteins had previously been shown to be necessary and sufficient to tether heterochromatin at the nuclear envelope. The lamin B receptor (Lbr) is expressed during development, but downregulates upon rod differentiation. A second tether is the intermediate filament lamin A (LA), which is not normally expressed in murine rods. Here, we show that in the rd1 model of retinitis pigmentosa, LA ectopically upregulates in rod photoreceptors at the onset of degeneration. LA upregulation correlated with increased heterochromatin tethering at the nuclear periphery in rd1 rods, suggesting that LA reorganizes the nucleus. To determine how heterochromatin tethering affects the genome, we used in vivo electroporation to misexpress LA or Lbr in mature rods in the absence of degeneration, resulting in the restoration of conventional nuclear architecture. Using scRNA-seq, we show that reorganizing the nucleus via LA/Lbr misexpression has relatively minor effects on rod gene expression. Next, using ATAC-seq, we show that LA and Lbr both lead to marked increases in genome accessibility. Novel ATAC-seq peaks tended to be associated with stress-responsive genes. Together, our data reveal that heterochromatin tethers have a global effect on genome accessibility, and suggest that heterochromatin tethering primes the photoreceptor genome to respond to stress.
2023-11-02 | GSE240312 | GEO
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:Gene positioning and regulation of nuclear architecture are thought to influence gene expression. Here, we show that in mouse olfactory neurons, silent olfactory receptor (OR) genes from different chromosomes converge in a small number of heterochromatic foci. These foci are OR-exclusive and form in a cell-type-specific and differentiation- dependent manner. The aggregation of OR genes is developmentally synchronous with the downregulation of Lamin b Receptor (LBR) and can be reversed by ectopic expression of LBR in mature olfactory neurons. LBR-induced reorganization of nuclear architecture and redistribution of OR loci results in misregulation of OR transcription and disruption of the targeting specificity of the olfactory neurons. Our observations are consistent with a model of spatial regulation of OR expression and provide evidence for the instructive role of nuclear architecture and compartmentalization in gene regulation and differentiation. A complex probe was made by array capture to label mouse olfactory receptor genes by DNA FISH; this microarray data verifies the composition of that probe. Probe was made by array capture and elution from a custom olfactory receptor genomic region tiling array. Probe was verified on a chr1-4 tiling array.
2012-08-30 | E-GEOD-38488 | 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. 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:We have characterised the product of a novel N terminal deletion of Lbr gene.
2021-09-10 | PXD024111 | Pride
Project description:The nuclear envelope protein Tm7sf2/NET47, a paralog of Lbr preferentially expressed in liver, was knocked out in mouse (C57/B6 background). The transcriptome of livers from WT and KO mice were compared by microarray.
2020-11-25 | GSE155762 | GEO