Nup93 modulates spatiotemporal dynamics and function of the HOXA gene cluster during differentiation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE130656 | GEO | 2021/12/06
REPOSITORIES: GEO
Similar Datasets
Project description:Total Proteome analysis of various AID degron-bearing DLD-1 cells ( Nup96, Nup62, Nup188, TPR, Nup93, GANP, PCID2, Nup153, Nup160, Nup205) before and after addition of Auxin for 4-8 h.
2023-03-31 | PXD039407 | Pride
Project description:Nuclear pore complexes (NPCs) are important for cellular functions beyond nucleocytoplasmic trafficking, including genome organization and gene expression. This multi-faceted nature and the slow turnover of NPC components complicates investigations of how individual nucleoporins act in these diverse processes. To address this question, we used an Auxin-Induced Degron (AID) system to distinguish roles of basket nucleoporins Nup153, Nup50 and Tpr. Here, we provide MS data for the Nuclear Pore-enriched fraction of human DLD-1 cells, expressing CRISPR-engeneered degron, fused with the endogenous locus of corresponding basket NUPs, in the absence or presence of Auxin.
2020-06-30 | PXD020075 | Pride
Project description:Nucleoporins (Nups) are a family of proteins best known as the constituent building blocks of nuclear pore complexes (NPCs), the transport channels that mediate nuclear transport. Recent evidence suggest that several Nups have additional roles in controlling the activation and silencing of developmental genes, however, the mechanistic details of these functions remain poorly understood. Here, we show that depletion of Nup153 in mouse embryonic stem cells (mESCs) causes the de-repression of developmental genes and induction of early differentiation. This loss of pluripotency is not associated with defects in global nucleo-cytoplasmic transport activity. Instead, Nup153 binds to the transcriptional start site (TSS) of developmental genes and mediates the recruitment of the polycomb repressive complex 1 (PRC1) to its target loci. Our results reveal a nuclear transport-independent role of Nup153 in maintaining stem cell pluripotency and introduce a role of NPC proteins in mammalian epigenetic gene silencing. RNA-seq, ChIP-Seq, and DamID-Seq for Nup153, Oct4, and key chromatin regulators in mouse ES cells and neural progenitors
2015-06-19 | E-GEOD-64008 | biostudies-arrayexpress
Project description:Nucleoporins (Nups) are a family of proteins best known as the constituent building blocks of nuclear pore complexes (NPCs), the transport channels that mediate nuclear transport. Recent evidence suggest that several Nups have additional roles in controlling the activation and silencing of developmental genes, however, the mechanistic details of these functions remain poorly understood. Here, we show that depletion of Nup153 in mouse embryonic stem cells (mESCs) causes the de-repression of developmental genes and induction of early differentiation. This loss of pluripotency is not associated with defects in global nucleo-cytoplasmic transport activity. Instead, Nup153 binds to the transcriptional start site (TSS) of developmental genes and mediates the recruitment of the polycomb repressive complex 1 (PRC1) to its target loci. Our results reveal a nuclear transport-independent role of Nup153 in maintaining stem cell pluripotency and introduce a role of NPC proteins in mammalian epigenetic gene silencing.
2015-06-19 | GSE64008 | GEO
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
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: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:We used RNA-seq approach to distinguish roles of basket nucleoporins Nup153, Nup50, and Tpr in transcription and nucleocytoplasmic trafficking. AID-mediated depletion of BSK-NUPs caused rapid and drastic changes in transcriptomic profiles within two hours of auxin addition. Changes upon Tpr nucleoporin loss were distinct from Nup153 and Nup50, but similar to changes upon loss of export factor NXF1 and GANP subunit of the TREX-2 mRNA export complex. Altogether, we demonstrated a unique role of Tpr nucleoporin in regulating genes expression through mRNA export.
2020-06-04 | GSE132363 | GEO
Project description:Nup133 belongs to the Y-complex, a key component of the nuclear pore complex (NPC) scaffold. Studies on a null mutation in mice previously revealed that Nup133 is essential for embryonic development but not for mouse embryonic stem cells (mESCs) proliferation. Using single pore detection and average NE-fluorescence intensity, we find that Nup133 is dispensable for interphase and postmitotic NPC scaffold assembly in pluripotent mESCs. However, loss of Nup133 specifically perturbs the formation of the nuclear basket as manifested by the absence of Tpr in about half of the NPCs combined with altered dynamics of Nup153. Nup153 is a large multifunctional protein that interacts with both the Y-complex and Tpr through its N-terminal NPC-targeting domain (NTD, [aa 1-339]) (Hase and Cordes, 2003; Vasu et al., 2001). To explore the possibility that the interaction between Nup153-NTD and the Y-complex or Tpr requires Nup133, we performed pull down assays on whole protein extracts from WT and Nup133-/- mESCs using recombinant Nup153-NTD [aa 1-339] as bait. Nup153 [aa 1-245], lacking the binding domains for the Y-complex and Tpr served as control. Western blot and quantitative mass spectrometry analyses detected Nup133 only in WT samples and documented its specific enrichment, along with other tested Y-Nups and Tpr, in the Nup153-NTD [aa 1-339] bound fraction. These analyses also revealed a similar enrichment of Tpr and Y-complex proteins in Nup153-NTD [aa 1-339]-purified extracts from either WT or Nup133-/- mESCs. These data show that in the context of whole cell lysates containing NPCs as dissociated subcomplexes, the lack of Nup133 neither precludes nor appreciably affects the biochemical interaction between Nup153-NTD and the Y-complex or Tpr. This differs from the in vivo situation that revealed a measurable impact of Nup133 on Nup153 dynamics and Tpr localization in the context of assembled NPCs. This apparent discrepancy between our in vitro and in vivo data indicates that the structural integrity of the NPC is likely required to visualize the contribution of Nup133 to the binding of Nup153 to Tpr or to the Y-complex. Hase, M.E., and Cordes, V.C. (2003). Direct interaction with nup153 mediates binding of Tpr to the periphery of the nuclear pore complex. Mol Biol Cell 14, 1923-1940. Vasu, S., Shah, S., Orjalo, A., Park, M., Fischer, W.H., and Forbes, D.J. (2001). Novel vertebrate nucleoporins Nup133 and Nup160 play a role in mRNA export. J Cell Biol 155, 339-354.
2018-05-28 | PXD009466 | Pride
Project description:Mechanical signals from the extracellular microenvironment have been shown to promote tumor and metastasis progression. It remains unclear how these signals are transmitted to the nucleus to regulate gene expression necessary for metastatic progression. In a genome-wide screen for metastasis-associated polymorphism in the non-coding regulatory region of the genome, we found NUP210, a nuclear pore complex protein as a metastasis susceptibility gene and a cellular mechanosensor. Depletion of NUP210 in metastatic cancer cells significantly reduces lung metastasis in mouse orthotopic transplantation models. Mechanistically, NUP210 interacts with histone H3.1/3.2 (preferentially enriched at the poised/bivalent gene promoters) at the nuclear periphery. To investigate how NUP210 regulates metastasis, we performed combined ChIP-seq and RNA-seq analysis to identify the NUP210-dependent downstream signaling pathways necessary for metastatic progression. Interestingly, RNA-seq analysis revealed that the loss of NUP210 in cancer cells significantly decreased the expression of mechanosensitive, cell adhesion/migration-related pro-metastatic genes. ChIP-seq analysis of H3K4me3 (transcriptional activation mark) and H3K27me3 (transcriptionally repressive, heterochromatin mark) in NUP210 WT/KO cells revealed that NUP210 loss resulted in increased heterochromatinization of mechanosensitive, cell migration-related genes associated at the nuclear periphery. Our results provide a new insight into the role of nuclear pore protein in regulating cellular mechanosensation and metastasis.
2021-03-05 | GSE146591 | GEO