Nuclear Pore Proteins in Regulation of Chromatin State

Kuhn, Terra M.; Capelson, Maya

doi:10.3390/cells8111414

Cited by 46 publications

(40 citation statements)

References 98 publications

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“…In cell-free extracts of Xenopus eggs that recapitulate nuclear assembly, the recruitment of Nup153 to the NE is dependent on the formation of the lamina (Smythe et al, 2000). TPR is also required to maintain the heterochromatin exclusion zones found at the NPCs (Krull et al, 2010) and all three nucleoporins are known to affect chromatin modification states (Kuhn and Capelson, 2019). The lamins are also closely associated with chromatin at the nuclear periphery and it is likely that peripheral chromatin is also playing a role in the association of lamins and NPCs and their distribution in the NE.…”

Section: Discussionmentioning

confidence: 99%

Computational analysis of lamin isoform interactions with nuclear pore complexes

Kittisopikul

Shimi

Tatli

et al. 2020

Preprint

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Nuclear lamin isoforms assemble into fibrous meshworks within the nuclear lamina 16 (NL) where they are associated with nuclear pore complexes (NPCs). Although the lamins and 17NPCs are major components of the nuclear envelope (NE), little is known about their structural 18 relationships. We used 3D structured illumination microscopy (3D-SIM) and sub-pixel image 19 analysis to show that NPCs are closely associated with lamin fibers in mouse embryonic 20 fibroblasts (MEFs). When lamin A/C (LA/C) or lamin B1 (LB1) are removed by gene knockout, the 21 NPCs retained their association and redistributed with the resulting enlarged lamin meshworks. 22 Cryo-ET revealed that more LA/C than LB1 fibers contacted the nucleoplasmic ring of NPCs. 23 Knockdown of the outer ring nucleoporin ELYS induced NPC clusters that excluded LA/C fibers. 24 Knockdown of the basket nucleoporin TPR reduced the size of LA/C, LB1, and LB2 meshworks 25 while retaining their close association with NPCs. NUP153 knockdown reduced LA/C and B2 26 meshwork size in wild type (WT) MEFs and caused NPC clustering in nuclei lacking LB1. Therefore, 27 lamins and nucleoporins act together to maintain the organization and distribution of lamin 28 meshworks and NPCs. 29 30 teins, the nuclear lamins, and nuclear pore complexes (NPCs) (Aebi et al., 1986; Fisher et al., 1986; 33 Goldman et al., 1986; McKeon et al., 1986). The four lamin isoforms LA, LC, LB1, and LB2 are mainly 34 associated with the inner nuclear membrane where they assemble into discrete meshworks of 35 fibers composing the nuclear lamina (NL). The NPCs penetrate the NE forming transport passage-36 ways delineated by the fusion of the inner and outer nuclear membranes, thereby allowing for 37 bidirectional transport across the NE. They are composed of multiple copies of 30 proteins known 38 1 of 27Manuscript to be submitted to eLife as nucleoporins (Beck and Hurt, 2016). Both the nuclear lamins and NPC structures are closely 39 associated with chromatin at the nuclear periphery (Guelen et al., 2008; Peric-Hupkes et al., 2010; 40 Ibarra and Hetzer, 2015). 41 The lamins are classified as A-type (LA, LC) and B-type (LB1, LB2). LA and LC are derived from 42 the Lmna gene by alternative splicing (Lin and Worman, 1993), whereas LB1 and LB2 are encoded 43 81 ity of the four lamin fiber meshworks and NPCs located within a thin layer at the nuclear surface. 82The results of our analyses demonstrate that NPCs are closely associated with lamin fibers. At 83 higher resolution cryo-ET confirms that both LA/C and LB1 filaments interact closely with the NPCs 84 at the nucleoplasmic ring. Targeted disruption of nucleoporins and lamin isoforms demonstrates 85 the interdependence of the spatial distributions of lamin fibers and NPCs. 86 2 of 27 Manuscript to be submitted to eLife WT WT Lmnb1 -/-Lmna -/-LA LB1 LB1 LA LB2 LC NPC NPC NPC NPC NPC NPC A B Figure 1. Co-Distribution of Lamin Fibers and NPCs. Colabeling of lamins and nuclear pore complexes in wt and lamin KO MEF nuclei using indire...

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Section: Discussionmentioning

confidence: 99%

Computational analysis of lamin isoform interactions with nuclear pore complexes

Kittisopikul

Shimi

Tatli

et al. 2020

Preprint

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“…These epigenetic modulations of chromatin are associated with changes in gene expression patterns [8, 32]. Molecules of the NE including lamins and many NETs and NPCs serve as anchoring sites for chromatin [9-11, 34]. A- and B-type lamins bind to chromatin through interactions with INM proteins containing the LAP2-emerin-MAN1 domain [12].…”

Section: Biologic Implications Of Chromatin Distribution In Malignantmentioning

confidence: 99%

Nuclear Morphology and the Biology of Cancer Cells

Fischer¹

2020

Acta Cytologica

121

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Background: For more than a century, diagnostic pathologists have used morphologic abnormalities of the nucleus as essential diagnostic features to distinguish benign from malignant cells. These features include nuclear enlargement and increased nuclear-to-cytoplasmic ratio, nuclear membrane irregularities, hyperchromasia, and abnormal chromatin distribution. As our knowledge about the genetic and epigenetic abnormalities of cancer cells has increased in recent decades, the pathophysiologic mechanisms that underlie these morphologic abnormalities remain incompletely understood. Summary: This review attempts to summarize biologic abnormalities in malignant cells related to these morphologic changes. The molecular anatomy of the nuclear envelope in normal and malignant cells is discussed as well as regulation of nuclear size and shape, regulation of signal transduction pathways by molecules of the nuclear envelope, chromatin distribution, and the effects of HPV infection on dysplastic cells in the uterine cervix. Key Message: Causes of morphologic nuclear abnormalities in malignant cells are likely multifactorial. They probably include mutations, dysregulation of signal transduction pathways, abnormal gene expression patterns, alterations of nuclear envelope proteins and chromatin, and aneuploidy.

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“…The involvement of Nups in these interactions with chromatin arouses a particular interest in Elys (embryonic large molecule derived from yolk sac), also known as Mel-28 (maternal effect lethal-28) or AHCTF1 (AT-hook containing transcription factor 1), as the Nup that can bind chromatin directly. Although several recently published reviews have described participation of Nups in chromatin organization [ 44 , 45 , 46 , 47 ], these papers did not focus on Elys. Here, I discuss the role that Elys plays in the post-mitotic NPC reassembly and in establishing and maintenance of overall genome architecture.…”

Section: Introductionmentioning

confidence: 99%

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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Nuclear Pore Proteins in Regulation of Chromatin State

Cited by 46 publications

References 98 publications

Computational analysis of lamin isoform interactions with nuclear pore complexes

Computational analysis of lamin isoform interactions with nuclear pore complexes

Nuclear Morphology and the Biology of Cancer Cells

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

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