Core Components of the Nuclear Pore Bind Distinct States of Chromatin and Contribute to Polycomb Repression

Gozalo, Alejandro; Duke, Ashley; Lan, Yemin; Pascual-Garcia, Pau; Talamas, Jessica A.; Nguyen, Son C.; Shah, Parisha P.; Jain, Rajan; Joyce, Eric F.; Capelson, Maya

doi:10.1016/j.molcel.2019.10.017

Cited by 78 publications

(111 citation statements)

References 86 publications

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“…The association of Nup98 mainly with promoters was also confirmed by the DamID approach in human cells [ 78 ]. Moreover, Nup107-interacting regions in Drosophila also mainly correspond to promoters or to other active chromatin regions [ 18 ].…”

Section: Genome-wide Interactions Of Elys and Other Nupsmentioning

confidence: 99%

“…NPCs are large multiprotein structures consisting of ~30 nucleoporins (Nups) each represented by 8–32 copies [ 1 ]. Apart from transport function, Nups interact with chromatin, thus affecting genome architecture and gene expression [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. While in yeast, the recruitment of genes to the NPCs causes their activation and is accompanied by the emergence of transcriptional memory [ 19 , 20 ], in higher eukaryotes the picture is more complicated.…”

Section: Introductionmentioning

confidence: 99%

“…In metazoans, some Nups are localized not only at the NE, but also in the nucleoplasm [ 21 , 22 , 23 ]. Moreover, while nucleoplasmic Nups bind to active genes promoting their transcription, the constituents of NPCs at the NE mostly interact with the silent genes, or those poised for activation [ 8 , 9 , 10 , 12 , 13 , 15 , 16 , 17 , 18 ]. In a similar fashion to yeast, the transcriptional memory was revealed in Drosophila and mammals.…”

Section: Introductionmentioning

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: Genome-wide Interactions Of Elys and Other Nupsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

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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“…It has also been reported that most of the tRNA loci, including the boundary element of pericentromeric heterochromatin, associate with Nup85 [117]. Moreover, the functional role of Drosophila Nup93, an inner ring Nups, in the silencing of Polycomb target genes was recently reported [159]. These cumulative pieces of evidence strongly suggest the involvement of NPC in the regulation of gene silencing in heterochromatic regions.…”

Section: Nucleoporins Modulate Gene Silencingmentioning

confidence: 89%

Nuclear Envelope Proteins Modulating the Heterochromatin Formation and Functions in Fission Yeast

Hirano

Asakawa

Sakuno

et al. 2020

Cells

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The nuclear envelope (NE) consists of the inner and outer nuclear membranes (INM and ONM), and the nuclear pore complex (NPC), which penetrates the double membrane. ONM continues with the endoplasmic reticulum (ER). INM and NPC can interact with chromatin to regulate the genetic activities of the chromosome. Studies in the fission yeast Schizosaccharomyces pombe have contributed to understanding the molecular mechanisms underlying heterochromatin formation by the RNAi-mediated and histone deacetylase machineries. Recent studies have demonstrated that NE proteins modulate heterochromatin formation and functions through interactions with heterochromatic regions, including the pericentromeric and the sub-telomeric regions. In this review, we first introduce the molecular mechanisms underlying the heterochromatin formation and functions in fission yeast, and then summarize the NE proteins that play a role in anchoring heterochromatic regions and in modulating heterochromatin formation and functions, highlighting roles for a conserved INM protein, Lem2.

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“…As such, the physical proximity of active HOXA cluster to a LAD anchored by the GLC seems counterintuitive. However, recent studies have shown that nuclear pore complexes (NPC) embedded at the nuclear periphery can associate with both enhancer and polycomb enriched regions 24,25 . In our effort to map NPC binding on chromatin, we observed a significant enrichment of the complex at both the active distal HOXA region as well as the GLC in OCI- Figure S7c).…”

Section: Main Textmentioning

confidence: 99%

Three-dimensional regulation ofHOXAcluster genes by acis-element in hematopoietic stem cell and leukemia

Gore

Himadewi

et al. 2020

Preprint

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Proper gene regulation is crucial for cellular differentiation, and dysregulation of key genes can lead to diseased states such as cancer. The HOX transcription factors play such a role during hematopoiesis, and aberrant expression of certain HOXA genes is found in certain acute myeloid leukemias (AMLs). While studies have shown that these genes are targeted by a variety of mutant proteins including mutant NPM1, MLL fusions, and NUP98 fusions, little is known about how long-range 3D chromatin interactions regulate the HOXA genes in normal hematopoiesis and leukemia. Here, we report the interaction between the HOXA cluster with a ~1.3 Mb upstream DNA methylation Canyon termed "Geneless Canyon" (GLC) in human CD34+/CD38-hematopoietic stem cells (HSCs) and AML cell lines. We show that CRISPR-Cas9 mediated deletion of the whole GLC region reduces the expression of the distal HOXA genes and compromises HSC and leukemia cells self-renewal. This long-range chromatin interaction brings the HOXA cluster in contact with the nuclear pore complex (NPC) at the nuclear periphery, which promotes HOXA gene expression and maintains HSC and leukemia cell self-renewal. These findings reveal how long-range 3D chromatin organization regulates key transcription factor genes in both normal and diseased hematopoietic cells.

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Core Components of the Nuclear Pore Bind Distinct States of Chromatin and Contribute to Polycomb Repression

Cited by 78 publications

References 86 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

Nuclear Envelope Proteins Modulating the Heterochromatin Formation and Functions in Fission Yeast

Three-dimensional regulation ofHOXAcluster genes by acis-element in hematopoietic stem cell and leukemia

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