Nucleoporin downregulation modulates keratinocyte differentiation independent of nuclear pore numbers
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ABSTRACT:
PROVIDER: PRJNA862059 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We determined the target gene sets controlled by NUP93 in maintaining in undifferentiated state of primary human keratinocytes.
2023-10-06 | GSE209655 | GEO
Project description:Nucleoporins (NUPs) comprise nuclear pore complexes, gateways for nucleocytoplasmic transport. As primary human keratinocytes switch from the progenitor state towards differentiation, most NUPs are strongly downregulated, with NUP93 being the most downregulated NUP in this process. To determine if this NUP downregulation is accompanied by a reduction in nuclear pore numbers, we leveraged Stochastic Optical Reconstruction Microscopy. No significant changes in nuclear pore numbers were detected using three independent NUP antibodies; however, NUP reduction in other subcellular compartments such as the cytoplasm was identified. To investigate how NUP reduction influences keratinocyte differentiation, we knocked down NUP93 in keratinocytes in the progenitor-state culture condition. NUP93 knockdown diminished keratinocytes' clonogenicity and epidermal regenerative capacity, without drastically affecting nuclear pore numbers or permeability. Using transcriptome profiling, we identified that NUP93 knockdown induces differentiation genes related to both mechanical and immune barrier functions, including the activation of known NF-κB target genes. Consistently, keratinocytes with NUP93 knockdown exhibited increased nuclear localization of the NF-κB p65/p50 transcription factors, and increased NF-κB reporter activity. Taken together, these findings highlight the gene regulatory roles contributed by differential NUP expression levels in keratinocyte differentiation, independent of nuclear pore numbers.
| S-EPMC10584948 | biostudies-literature
Project description:Nuclear pores are essential pathways for nuclear-cytoplasmic transport of molecules. Whether and how cells change nuclear pores to alter nuclear transport and cellular function is unknown. Here, we show that heart muscle cells (cardiomyocytes) undergo a 63% decrease in nuclear pore numbers during differentiation, which alters their response to extracellular signals. This maturation-associated decline in nuclear pore numbers per nucleus is associated with lower nuclear levels and import of Mitogen-activated Protein Kinase (MAPK) signaling proteins. Experimental reduction of nuclear pore numbers decreased nuclear import of MAPK signaling proteins. In a mouse model of high blood pressure, reduction of cardiomyocyte nuclear pore numbers reduced adverse heart remodeling and gene regulation, which reduced progression to lethal heart failure. The observed decrease in nuclear pore numbers in cardiomyocyte differentiation and resulting functional changes suggest a paradigm by which terminally differentiated cells could permanently alter their handling of information flux across the nuclear envelope and, with that, their behavior.
2022-09-26 | GSE186949 | GEO
Project description:Nucleoporin 153 links nuclear pore complex to chromatin architecture by mediating CTCF and cohesin binding
| PRJNA559545 | ENA
Project description:Establishment of cell lineage specification, maintenance of cellular states and cellular responses to developmental cues rely on gene regulation and spatial genome organization during early development. Emerging data point to highly coordinated activity between epigenetic mechanisms that involve nuclear architecture, chromatin structure and chromatin organization. We show that the nuclear pore complex (NPC) basket protein, Nucleoporin 153 (NUP153) interacts with the nuclear architectural proteins, CTCF and cohesin, and mediates their binding across cis-regulatory elements in pluripotent mouse embryonic stem (ES) cells. NUP153 depletion results in altered occupancy of architectural proteins coupled with differential changes in transcription. This affect is most prevalent at the bivalent genes. To provide molecular insights onto NUP153-mediated gene regulation, we utilized Epidermal Growth Factor (EGF)-inducible immediate early gene (IEG) loci, which we identified as NUP153 targets. IEG transcription is regulated through a POL II pause-release mechanism. We provide evidence that NUP153 is critical for CTCF and cohesin occupancy and subsequent POL II recruitment to the IEG proximal-promoter sites during the paused state. In particular, establishment of a poised IEG chromatin environment relies on co-regulatory function of NUP153 and CTCF, which underlies efficient and timely IEG transcription at the NPC. Our results uncover a key role for the mammalian NPC in distribution of chromatin architectural proteins and demonstrate that NUP153 acts as a cis-acting factor that causally links the NPC to chromatin organization during transcription regulation.
2020-05-21 | GSE135646 | GEO
Project description:Establishment of cell lineage specification, maintenance of cellular states and cellular responses to developmental cues rely on gene regulation and spatial genome organization during early development. Emerging data point to highly coordinated activity between epigenetic mechanisms that involve nuclear architecture, chromatin structure and chromatin organization. We show that the nuclear pore complex (NPC) basket protein, Nucleoporin 153 (NUP153) interacts with the nuclear architectural proteins, CTCF and cohesin, and mediates their binding across cis-regulatory elements in pluripotent mouse embryonic stem (ES) cells. NUP153 depletion results in altered occupancy of architectural proteins coupled with differential changes in transcription. This affect is most prevalent at the bivalent genes. To provide molecular insights onto NUP153-mediated gene regulation, we utilized Epidermal Growth Factor (EGF)-inducible immediate early gene (IEG) loci, which we identified as NUP153 targets. IEG transcription is regulated through a POL II pause-release mechanism. We provide evidence that NUP153 is critical for CTCF and cohesin occupancy and subsequent POL II recruitment to the IEG proximal-promoter sites during the paused state. In particular, establishment of a poised IEG chromatin environment relies on co-regulatory function of NUP153 and CTCF, which underlies efficient and timely IEG transcription at the NPC. Our results uncover a key role for the mammalian NPC in distribution of chromatin architectural proteins and demonstrate that NUP153 acts as a cis-acting factor that causally links the NPC to chromatin organization during transcription regulation.
2020-05-21 | GSE135645 | GEO
Project description:Nucleoporin 153 links nuclear pore complex to chromatin architecture by mediating CTCF and cohesin binding [RNA-Seq]
| PRJNA559548 | ENA
Project description:Nucleoporin 153 links nuclear pore complex to chromatin architecture by mediating CTCF and cohesin binding (ChIP-Seq)
| PRJNA559549 | ENA
Project description:Previous BioID experiments targeting the nucleoporin (NUP) NUP158 (PMID: 36410438; PXD031245), as well as NUP110, NUP76 and NUP96 (PMID: 39206942; PXD047268) indicated that proximity labelling delivers highly specific interactome data in the confined localisation of the nuclear pore, with a labelling radius well below the size of the nuclear pore. The resulting proximity data allowed to assign NUPs and nuclear transport factors to specific subregions of the pore. Here we extended this approach to target NUP75 and transport factors MEX67 and Ran.
2024-09-20 | PXD055934 | Pride
Project description:The organization of the genome in the three-dimensional space of the nucleus is coupled with cell type-specific gene expression. However, how nuclear architecture influences transcription that governs cell identity remains unknown. Here, we show that Nuclear Pore Complex (NPC) components Nup93 and Nup153 bind super-enhancers (SE), regulatory structures that drive the expression of key genes that specify cell identity. We found that nucleoporin-associated SEs localize preferentially to the nuclear periphery, and absence of Nup153 and Nup93 results in dramatic transcriptional changes of SE-associated genes. Our results reveal a crucial role of NPC components in the regulation of cell type specifying genes and highlight nuclear architecture as a regulatory layer of genome functions in cell fate.
2016-11-15 | GSE87831 | GEO