Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The role of nuclear pores in gene regulation, development and disease.

ABSTRACT: Nuclear-pore complexes (NPCs) are large protein channels that span the nuclear envelope (NE), which is a double membrane that encloses the nuclear genome of eukaryotes. Each of the typically 2,000-4,000 pores in the NE of vertebrate cells is composed of multiple copies of 30 different proteins known as nucleoporins. The evolutionarily conserved NPC proteins have the well-characterized function of mediating the transport of molecules between the nucleoplasm and the cytoplasm. Mutations in nucleoporins are often linked to specific developmental defects and disease, and the resulting phenotypes are usually interpreted as the consequences of perturbed nuclear transport activity. However, recent evidence suggests that NPCs have additional functions in chromatin organization and gene regulation, some of which might be independent of nuclear transport. Here, we review the transport-dependent and transport-independent roles of NPCs in the regulation of nuclear function and gene expression.

SUBMITTER: Capelson M

PROVIDER: S-EPMC2727434 | biostudies-other | 2009 Jul

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Pre-assembled Nuclear Pores Insert into the Nuclear Envelope during Early Development.

Project description:Nuclear pore complexes (NPCs) span the nuclear envelope (NE) and mediate nucleocytoplasmic transport. In metazoan oocytes and early embryos, NPCs reside not only within the NE, but also at some endoplasmic reticulum (ER) membrane sheets, termed annulate lamellae (AL). Although a role for AL as NPC storage pools has been discussed, it remains controversial whether and how they contribute to the NPC density at the NE. Here, we show that AL insert into the NE as the ER feeds rapid nuclear expansion in Drosophila blastoderm embryos. We demonstrate that NPCs within AL resemble pore scaffolds that mature only upon insertion into the NE. We delineate a topological model in which NE openings are critical for AL uptake that nevertheless occurs without compromising the permeability barrier of the NE. We finally show that this unanticipated mode of pore insertion is developmentally regulated and operates prior to gastrulation.

| S-EPMC4967450 | biostudies-literature

Regulation of Cenp-F localization to nuclear pores and kinetochores.

Project description:In metazoans, the assembly of kinetochores on centrometric chromatin and the dismantling of nuclear pore complexes are processes that have to be tightly coordinated to ensure the proper assembly of the mitotic spindle and a successful mitosis. It is therefore noteworthy that these two macromolecular assemblies share a subset of constituents. One of these multifaceted components is Cenp-F, a protein implicated in cancer and developmental pathologies. During the cell cycle, Cenp-F localizes in multiple cellular structures including the nuclear envelope in late G2/early prophase and kinetochores throughout mitosis. We recently characterized the molecular determinants of Cenp-F interaction with Nup133, a structural nuclear pore constituent. In parallel with two other independent studies, we further elucidated the mechanisms governing Cenp-F kinetochore recruitment that mainly relies on its interaction with Bub1, with redundant contribution of Cenp-E upon acute microtubule depolymerisation. Here we synthesize the current literature regarding the dual location of Cenp-F at nuclear pores and kinetochores and extend our discussion to the regulation of these NPC and kinetochore localizations by mitotic kinase and spindle microtubules.

| S-EPMC6260214 | biostudies-literature

Pre-assembled Nuclear Pores Insert into the Nuclear Envelope During Early Development

Project description:Nuclear Pore Complexes (NPCs) span the nuclear envelope (NE) and mediate nucleocytoplasmic transport. In metazoan oocytes and early embryos, NPCs not only reside within the NE but also at some endoplasmatic reticulum (ER) membrane sheets, termed annulate lamellae (AL). Although a role for AL as NPC storage pools has been discussed, it remains controversial if and how they contribute to the NPC density at the NE. Here we show that AL insert into the NE as the ER feeds rapid nuclear expansion in Drosophila blastoderm embryos. We demonstrate that NPCs within AL resemble pore scaffolds that mature only upon insertion into the NE. We delineate a topological model in which NE openings are critical for AL uptake that nevertheless occurs without compromising the permeability barrier of the NE. We finally show that this unanticipated mode of pore insertion is developmentally regulated and operates prior to gastrulation.

2016-07-12 | PXD004120 | Pride

Regulation of recombination at yeast nuclear pores controls repair and triplet repeat stability.

Project description:Secondary structure-forming DNA sequences such as CAG repeats interfere with replication and repair, provoking fork stalling, chromosome fragility, and recombination. In budding yeast, we found that expanded CAG repeats are more likely than unexpanded repeats to localize to the nuclear periphery. This positioning is transient, occurs in late S phase, requires replication, and is associated with decreased subnuclear mobility of the locus. In contrast to persistent double-stranded breaks, expanded CAG repeats at the nuclear envelope associate with pores but not with the inner nuclear membrane protein Mps3. Relocation requires Nup84 and the Slx5/8 SUMO-dependent ubiquitin ligase but not Rad51, Mec1, or Tel1. Importantly, the presence of the Nup84 pore subcomplex and Slx5/8 suppresses CAG repeat fragility and instability. Repeat instability in nup84, slx5, or slx8 mutant cells arises through aberrant homologous recombination and is distinct from instability arising from the loss of ligase 4-dependent end-joining. Genetic and physical analysis of Rad52 sumoylation and binding at the CAG tract suggests that Slx5/8 targets sumoylated Rad52 for degradation at the pore to facilitate recovery from acute replication stress by promoting replication fork restart. We thereby confirmed that the relocation of damage to nuclear pores plays an important role in a naturally occurring repair process.

| S-EPMC4441049 | biostudies-literature

Role of histone deacetylases in gene regulation at nuclear lamina.

Project description:Theoretical models suggest that gene silencing at the nuclear periphery may involve "closing" of chromatin by transcriptional repressors, such as histone deacetylases (HDACs). Here we provide experimental evidence confirming these predictions. Histone acetylation, chromatin compactness, and gene repression in lamina-interacting multigenic chromatin domains were analyzed in Drosophila S2 cells in which B-type lamin, diverse HDACs, and lamina-associated proteins were downregulated by dsRNA. Lamin depletion resulted in decreased compactness of the repressed multigenic domain associated with its detachment from the lamina and enhanced histone acetylation. Our data reveal the major role for HDAC1 in mediating deacetylation, chromatin compaction, and gene silencing in the multigenic domain, and an auxiliary role for HDAC3 that is required for retention of the domain at the lamina. These findings demonstrate the manifold and central involvement of class I HDACs in regulation of lamina-associated genes, illuminating a mechanism by which these enzymes can orchestrate normal and pathological development.

| S-EPMC3511463 | biostudies-literature

Nuclear Pores Regulate Muscle Development and Maintenance by Assembling a Localized Mef2C Complex.

Project description:Nuclear pore complexes (NPCs) are multiprotein channels connecting the nucleus with the cytoplasm. NPCs have been shown to have tissue-specific composition, suggesting that their function can be specialized. However, the physiological roles of NPC composition changes and their impacts on cellular processes remain unclear. Here we show that the addition of the Nup210 nucleoporin to NPCs during myoblast differentiation results in assembly of an Mef2C transcriptional complex required for efficient expression of muscle structural genes and microRNAs. We show that this NPC-localized complex is essential for muscle growth, myofiber maturation, and muscle cell survival and that alterations in its activity result in muscle degeneration. Our findings suggest that NPCs regulate the activity of functional gene groups by acting as scaffolds that promote the local assembly of tissue-specific transcription complexes and show how nuclear pore composition changes can be exploited to regulate gene expression at the nuclear periphery.

| S-EPMC5515297 | biostudies-literature

Nuclear pores. Architecture of the nuclear pore complex coat.

Project description:The nuclear pore complex (NPC) constitutes the sole gateway for bidirectional nucleocytoplasmic transport. Despite half a century of structural characterization, the architecture of the NPC remains unknown. Here we present the crystal structure of a reconstituted ~400-kilodalton coat nucleoporin complex (CNC) from Saccharomyces cerevisiae at a 7.4 angstrom resolution. The crystal structure revealed a curved Y-shaped architecture and the molecular details of the coat nucleoporin interactions forming the central "triskelion" of the Y. A structural comparison of the yeast CNC with an electron microscopy reconstruction of its human counterpart suggested the evolutionary conservation of the elucidated architecture. Moreover, 32 copies of the CNC crystal structure docked readily into a cryoelectron tomographic reconstruction of the fully assembled human NPC, thereby accounting for ~16 megadalton of its mass.

| S-EPMC5180592 | biostudies-literature

The role of nuclear bodies in gene expression and disease.

Project description:This review summarizes the current understanding of the role of nuclear bodies in regulating gene expression. The compartmentalization of cellular processes, such as ribosome biogenesis, RNA processing, cellular response to stress, transcription, modification and assembly of spliceosomal snRNPs, histone gene synthesis and nuclear RNA retention, has significant implications for gene regulation. These functional nuclear domains include the nucleolus, nuclear speckle, nuclear stress body, transcription factory, Cajal body, Gemini of Cajal body, histone locus body and paraspeckle. We herein review the roles of nuclear bodies in regulating gene expression and their relation to human health and disease.

| S-EPMC3771687 | biostudies-literature

Nuclear transport surveillance of p53 by nuclear pores in glioblastoma

Project description:Nuclear pore complexes (NPCs) are the central apparatus of nucleocytoplasmic transport. Disease-specific alterations of NPCs contribute to the pathogenesis of many cancers; however, the roles of NPCs in glioblastoma (GBM) are unknown. In this study, we report genomic amplification of NUP107, a component of NPCs, in GBM and show that NUP107 is overexpressed simultaneously with MDM2, a critical E3 ligase that mediates p53 degradation. Depletion of NUP107 inhibits the growth of GBM cell lines through p53 protein stabilization. Mechanistically, NPCs establish a p53 degradation platform via an export pathway coupled with 26S proteasome tethering. NUP107 is the keystone for NPC assembly; the loss of NUP107 affects the integrity of the NPC structure, and thus the proportion of 26S proteasome in the vicinity of nuclear pores significantly decreases. Together, our findings establish roles of NPCs in transport surveillance and provide insights into p53 inactivation in GBM.

2023-08-19 | GSE216888 | GEO

Nuclear lamin phosphorylation: an emerging role in gene regulation and pathogenesis of laminopathies.

Project description:Decades of studies have established that nuclear lamin polymers form the nuclear lamina, a protein meshwork that supports the nuclear envelope structure and tethers heterochromatin to the nuclear periphery. Much less is known about unpolymerized nuclear lamins in the nuclear interior, some of which are now known to undergo specific phosphorylation. A recent finding that phosphorylated lamins bind gene enhancer regions offers a new hypothesis that lamin phosphorylation may influence transcriptional regulation in the nuclear interior. In this review, we discuss the regulation, localization, and functions of phosphorylated lamins. We summarize kinases that phosphorylate lamins in a variety of biological contexts. Our discussion extends to laminopathies, a spectrum of degenerative disorders caused by lamin gene mutations, such as cardiomyopathies and progeria. We compare the prevailing hypothesis for laminopathy pathogenesis based on lamins' function at the nuclear lamina with an emerging hypothesis based on phosphorylated lamins' function in the nuclear interior.

| S-EPMC7588210 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data