Nucleoporin 153 links nuclear pore complex to chromatin architecture by mediating CTCF and cohesin binding

Kadota, Shinichi; Ou, Jianhong; Shi, Yuqian; Lee, Jeannie T.; Sun, Jiayu; Yildirim, E.

doi:10.1038/s41467-020-16394-3

Cited by 59 publications

(59 citation statements)

References 70 publications

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“…These findings support a mechanistic model whereby NPC-anchored enhancer-promoter looping of poised genes, preserved after removal of an inductor, may facilitate more rapid reactivation of these genes in response to external stimuli [ 16 ] ( Figure 3 c). A similar model was recently suggested to explain rapid activation of immediate early gene transcription in response to an induction by epidermal growth factor in HeLa cells [ 81 ]. In this case, the NPC-linked Nup153 controls binding of CTCF and cohesin with the promoter and enhancer of uninduced gene, leading to RNA polymerase II pausing on its promoter.…”

Section: Influence Of Elys and Other Nups On Gene Expressionmentioning

confidence: 78%

“…However, as a dynamic Nup [ 22 ], it may also interact with chromatin in the nuclear interior. Mapping of Nup153-interacting regions in mammalian genomes by DamID or ChIP-seq has shown that, depending on cell type, Nup153 may interact with the active H3K27 acetylated chromatin of super enhancers [ 15 ], with the inactive Pc-repressed chromatin of developmental genes [ 14 ], with the promoters and 3′-ends of Sox2-regulated genes [ 80 ], or with active and inactive promoters, as well as with enhancers and boundaries between topologically associating domains (TADs) [ 81 ]. Nup153-genome interactions take place both at the NE and in the nucleoplasm.…”

Section: Genome-wide Interactions Of Elys and Other Nupsmentioning

confidence: 99%

“…Nup153-genome interactions take place both at the NE and in the nucleoplasm. Consistent with its enrichment at TAD boundaries, Nup153 was shown to physically associate with cohesin and CCCTC-binding factor (CTCF) [ 81 ], the proteins which participate in TAD formation in mammals through the loop extrusion mechanism [ 82 , 83 , 84 ]. However, the impact of Nup153 (or other Nups) on TAD formation has not yet been examined.…”

Section: Genome-wide Interactions Of Elys and Other Nupsmentioning

confidence: 99%

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The Role of Nucleoporin Elys in Nuclear Pore Complex Assembly and Regulation of Genome Architecture

Shevelyov

2020

IJMS

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For a long time, the nuclear lamina was thought to be the sole scaffold for the attachment of chromosomes to the nuclear envelope (NE) in metazoans. However, accumulating evidence indicates that nuclear pore complexes (NPCs) comprised of nucleoporins (Nups) participate in this process as well. One of the Nups, Elys, initiates NPC reassembly at the end of mitosis. Elys directly binds the decondensing chromatin and interacts with the Nup107–160 subcomplex of NPCs, thus serving as a seeding point for the subsequent recruitment of other NPC subcomplexes and connecting chromatin with the re-forming NE. Recent studies also uncovered the important functions of Elys during interphase where it interacts with chromatin and affects its compactness. Therefore, Elys seems to be one of the key Nups regulating chromatin organization. This review summarizes the current state of our knowledge about the participation of Elys in the post-mitotic NPC reassembly as well as the role that Elys and other Nups play in the maintenance of genome architecture.

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Section: Influence Of Elys and Other Nups On Gene Expressionmentioning

confidence: 78%

Section: Genome-wide Interactions Of Elys and Other Nupsmentioning

confidence: 99%

Section: Genome-wide Interactions Of Elys and Other Nupsmentioning

confidence: 99%

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The Role of Nucleoporin Elys in Nuclear Pore Complex Assembly and Regulation of Genome Architecture

Shevelyov

2020

IJMS

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“…While a critical role in transcription has been assigned to components of the nuclear pore basket, which are closest to the the genome [11,[23][24][25][26], gene expression has also been reported to depend on the core NPC scaffold [9,27,28], including the Y-complex (a.k.a. the Nup84 complex in budding yeast).…”

Section: Introductionmentioning

confidence: 99%

A nuclear pore sub-complex restricts the propagation of Ty retrotransposons by limiting their transcription

Bonnet

Chaput

Palancade

et al. 2021

Preprint

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Beyond their canonical function in nucleocytoplasmic exchanges, nuclear pore complexes (NPCs) regulate the expression of protein-coding genes. Here, we have implemented transcriptomic and molecular methods to specifically address the impact of the NPC on retroelements, which are present in multiple copies in genomes. We report a novel function for the Nup84 complex, a core NPC building block, in specifically restricting the transcription of LTR-retrotransposons in yeast. Nup84 complex-dependent repression impacts both Copia and Gypsy Ty LTR-retrotransposons, all over the S. cerevisiae genome. Mechanistically, the Nup84 complex restricts the transcription of Ty1, the most active yeast retrotransposon, through the tethering of the SUMO-deconjugating enzyme Ulp1 to NPCs. Strikingly, the modest accumulation of Ty1 RNAs caused by Nup84 complex loss-of-function is sufficient to trigger an important increase of Ty1 cDNA levels, resulting in massive Ty1 retrotransposition. Altogether, our studies expand our understanding of the complex interactions between retrotransposons and the NPC, and highlight the importance for the cells to keep retrotransposon under tight transcriptional control.AUTHOR SUMMARYRetroelements, which replicate by reverse transcription of their RNA into a cDNA that is integrated into the host genetic material, play an important role in the plasticity of eukaryotic genomes. The study of yeast retrotransposons has led to the identification of host factors that limit retroelement mobility, including components of the nuclear pore complex (NPC), most of them still awaiting mechanistic characterization. Here, we investigated the contribution of the Nup84 complex, a core NPC scaffold, to retrotransposon biology in budding yeast. Our findings uncover that the Nup84 complex restricts the transcription of phylogenetically-distinct Ty retroelements. By focusing on Ty1 retrotransposons, we provide evidence that repression by the Nup84 complex depends on the maintenance at the NPC of the SUMO-protease Ulp1, an essential enzyme of the SUMO pathway with multiple targets in the transcription machinery. We finally show that this transcriptional control is critical for genome dynamics, since a small increase in the accumulation of Ty1 RNAs leads to massive retrotransposition. Our data reveal that although relatively abundant, Ty transcripts are limiting for retrotransposition, underscoring the importance of a tight control of their expression. They also characterize a new non-canonical function of NPCs, confirming their connection with genome expression and stability.

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“…For example, Y-complex Nup components ELYS and Sec13 (Figure 2 ) can alter chromatin functionality via interacting with chromatin remodeling complexes ( 169 ). Nup153 was recently shown to effect chromatin organization via interacting with architectural proteins CTCF (CCCTC-binding factor) and cohesion ( 170 ). Given that Nup153 and CPSF6 share the same binding pocket on CA (Figure 4C and D ), additional work is required to discern whether regulating the CA-CPSF6 interaction or perhaps a novel pathway involving CTCF/cohesion underlies Nup153’s role in HIV-1 integration site targeting.…”

Section: Introductionmentioning

confidence: 99%

Factors that mold the nuclear landscape of HIV-1 integration

Bedwell

Engelman

2020

Nucleic Acids Research

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The integration of retroviral reverse transcripts into the chromatin of the cells that they infect is required for virus replication. Retroviral integration has far-reaching consequences, from perpetuating deadly human diseases to molding metazoan evolution. The lentivirus human immunodeficiency virus 1 (HIV-1), which is the causative agent of the AIDS pandemic, efficiently infects interphase cells due to the active nuclear import of its preintegration complex (PIC). To enable integration, the PIC must navigate the densely-packed nuclear environment where the genome is organized into different chromatin states of varying accessibility in accordance with cellular needs. The HIV-1 capsid protein interacts with specific host factors to facilitate PIC nuclear import, while additional interactions of viral integrase, the enzyme responsible for viral DNA integration, with cellular nuclear proteins and nucleobases guide integration to specific chromosomal sites. HIV-1 integration favors transcriptionally active chromatin such as speckle-associated domains and disfavors heterochromatin including lamina-associated domains. In this review, we describe virus-host interactions that facilitate HIV-1 PIC nuclear import and integration site targeting, highlighting commonalities among factors that participate in both of these steps. We moreover discuss how the nuclear landscape influences HIV-1 integration site selection as well as the establishment of active versus latent virus infection.

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Nucleoporin 153 links nuclear pore complex to chromatin architecture by mediating CTCF and cohesin binding

Cited by 59 publications

References 70 publications

The Role of Nucleoporin Elys in Nuclear Pore Complex Assembly and Regulation of Genome Architecture

The Role of Nucleoporin Elys in Nuclear Pore Complex Assembly and Regulation of Genome Architecture

A nuclear pore sub-complex restricts the propagation of Ty retrotransposons by limiting their transcription

Factors that mold the nuclear landscape of HIV-1 integration

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