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Nucleoporin Nup153 Regulates Stem Cell Pluripotency through Gene Silencing

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE64008 | GEO | 2015/06/19

SECONDARY ACCESSION(S): PRJNA269747

REPOSITORIES: GEO

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Nucleoporin Nup153 Regulates Stem Cell Pluripotency through Gene Silencing

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

Nup93 modulates spatiotemporal dynamics and function of the HOXA gene cluster during differentiation

Project description:The central role of nucleoporins is to transport RNA and proteins. In addtion, nucleoporins are also involved in gene regulation. Furthermore, nucleoporins - Nup93, Nup153, Nup98 and Nup210, directly associate with developmental genes and regulate developmental processes by direct association with developmental genes. Here, we identified genome wide binding profile of Nup93 - a core component of the nuclear pore complex in colorectal cancer cell line DLD-1 by ChIP-seq. Our ChIP-seq analysis revealed significant association of Nup93 with developmental genes and known enhancer marks such as H3K4me1 and H3K27Ac . We found that Nup93 shares binding sites with CTCF - the well known chromatin organizer, suggesting a functional overlap between Nup93 and CTCF in the organization and regulation of developmental gene expression such as the the HOXA gene cluster.

2021-12-06 | GSE130656 | GEO

Knockdown of NUP62 of human head and neck squamous cell carcinoma cell line UMSCC1

Project description:p63, especially its dominant isoform ∆Np63⍺, plays essential roles in squamous cell carcinomas (SCCs); yet the mechanisms controlling its nuclear transport remain unknown. Nucleoporins (NUPs) are a family of proteins building nuclear pore complex (NPC) and mediating nuclear transport across the nuclear envelope. Recent evidence suggests a cell-type-specific function for certain NUPs; however, the significance of NUPs in SCC biology remains unknown. In this study, we report that nucleoporin 62 (NUP62) is highly expressed in stratified squamous epithelia, which is further elevated in SCCs. Depletion of NUP62 inhibited the proliferation ability and augmented differentiation characteristics of SCC cells. This loss of dedifferentiation status was associated with defects in ∆Np63⍺ nuclear transport. We further found that differentiation inducible Rho kinase reduced an interaction between NUP62 and ∆Np63a by phosphorylation of phenylalanine-glycine regions of NUP62, resulting in attenuated ∆Np63⍺ nuclear import. Our results characterize NUP62 as a key gatekeeper for ∆Np63⍺ and uncover its significant function to control ∆Np63⍺ nuclear transport in SCC.

2017-11-16 | GSE103991 | GEO

Gene expression profiling of human DLD-1 cells after instant depletion of basket nucleoporins

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

Distinct Basket Nucleoporins roles in Nuclear Pore Function and Gene Expression

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

Association of NUP153 on genomic DNA in TE5 cells [ChIP-seq]

Project description:To understand the regulatory regions of genomic DNA by nuclear pore, the genomic region associated by NUP153, one of nuclear pore protein, was determined by Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) .

2023-04-01 | GSE200715 | GEO

Nucleoporin 153 links nuclear pore complex to chromatin architecture by mediating CTCF and cohesin binding (ChIP-Seq)

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

Nucleoporin 153 links nuclear pore complex to chromatin architecture by mediating CTCF and cohesin binding [RNA-Seq]

2020-05-21 | GSE135645 | GEO

Nucleoporin-mediated regulation of cell identity genes

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

Nup153 defines neural identity through cooperative transcriptional control with Sox2

Project description:Through RNA interference and genome-wide Nup153 binding studies, we found that Nup153 and Sox2 bind and co-regulate hundreds of genes. Furthermore, we found that Nup153 exhibits binding location dependent spatially distinct transcriptional control by differentially regulating expression when bound to the promoter region or to the transcription end site (TES). These results establish Nup153 not only as a novel transcriptional co-regulator of Sox2 but also as a key player in the regulation of cell fate by directly modulating gene expression.

2017-09-14 | GSE99783 | GEO

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