High-precision mapping of nuclear pore-chromatin interactions reveals new principles of genome organization at the nuclear envelope
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ABSTRACT:
PROVIDER: PRJNA735264 | ENA |
REPOSITORIES: ENA
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Project description:The role of nuclear pore complexes (NPCs) in genome organization remains poorly characterized due to technical limitations in probing genome-wide protein-DNA interactions that are specific to the nuclear envelope. Here, we developed a sensitive method, NPC-DamID, which combines in vitro reconstitution of nuclear import and DamID technology. This fixation-free method specifically identifies genomic DNA interactions at the NPCs in intact nuclei. We found that NPCs are preferentially associated with common and hierarchically arranged super-enhancers (SEs) across multiple cells and tissue types. We also uncovered phase-separated condensates at NPCs that compartmentalize and concentrate transcriptional coactivators and structural proteins at SE-regulated genes. Our results support the idea that NPCs are sites of anchoring SE regulatory hubs through their interaction with CTCF and also maintains the conformation of SEs through interaction with structural proteins of SEs like Med1 and PolII.
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Project description:Nuclear pores are essential pathways for nuclear-cytoplasmic transport of molecules. Whether and how cells change nuclear pores to alter nuclear transport and cellular function is unknown. Here, we show that heart muscle cells (cardiomyocytes) undergo a 63% decrease in nuclear pore numbers during differentiation, which alters their response to extracellular signals. This maturation-associated decline in nuclear pore numbers per nucleus is associated with lower nuclear levels and import of Mitogen-activated Protein Kinase (MAPK) signaling proteins. Experimental reduction of nuclear pore numbers decreased nuclear import of MAPK signaling proteins. In a mouse model of high blood pressure, reduction of cardiomyocyte nuclear pore numbers reduced adverse heart remodeling and gene regulation, which reduced progression to lethal heart failure. The observed decrease in nuclear pore numbers in cardiomyocyte differentiation and resulting functional changes suggest a paradigm by which terminally differentiated cells could permanently alter their handling of information flux across the nuclear envelope and, with that, their behavior.
2022-09-26 | GSE186949 | GEO
Project description:We used biochemical fractionation coupled with the subtractive proteomics to profile PNET proteins. Both the crude NE and the total MM fraction were subject to label-free quantitative mass spectrometry (LFQMS). We also adapted proximity labeling-coupled LFQMS (PL-LFQMS) method to map the PNET proteome. Overall, We identified over 200 potential candidates for plant nuclear envelope transmembrane (PNET) proteins and confirmed 14 PNETs.
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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
Project description:Nuclear pore complexes (NPCs) are giant cylindrical structures embedded into the nuclear envelope and mediate nucleocytoplasmic exchange. NPC longevity has been linked to aging but since they appear to rarely turn over, the underlying mechanisms remain understudied. Here, we show that upon nitrogen starvation and genetic interference with NPC architecture, Nups are rapidly degraded in budding yeast. We demonstrate that NPC turnover involves 25 vacuolar proteases and the core autophagic machinery. Autophagic degradation is mediated by the cytoplasmically exposed Nup159 that serves as intrinsic cargo receptor and directly binds to the autophagic marker protein Atg8. The inducible manner of this mechanism might explain why NPCs are long-lived under specific conditions
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Project description:Lamins and transmembrane proteins within the nuclear envelope regulate nuclear structure and chromatin organization. Nuclear Envelope Transmembrane Protein 39 (Net39) is muscle nuclear envelope protein whose functions in vivo have not been explored. We show that mice lacking Net39 succumb to severe myopathy and juvenile lethality, with concomitant disruption in nuclear integrity, chromatin accessibility, gene expression and metabolism. These abnormalities resemble those of Emery-Dreifuss muscular dystrophy (EDMD), caused by mutations in A-type Lamins (LMNA) and other genes, like Emerin (EMD). We observe that Net39 is downregulated in EDMD patients, implicating Net39 in the pathogenesis of this disorder. Our findings highlight the role of Net39 at the nuclear envelope in maintaining muscle chromatin organization, gene expression and function, and its potential contribution to the molecular etiology of EDMD.
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Project description:We investigate the transcription and export of the uni-strand piRNA cluster flamenco and report the involvement of Nuclear Pore Complex subunits in its nuclear export and specification as a piRNA precursor.
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Project description:Lamins and transmembrane proteins within the nuclear envelope are regulators of nuclear structure and chromatin organization. Nuclear Envelope Transmembrane Protein 39 (Net39) is a muscle-restricted nuclear envelope protein. We show that mice lacking Net39 succumb to severe myopathy and neonatal lethality, with concomitant disruption in nuclear integrity, chromatin accessibility, gene expression and metabolism. These abnormalities resemble those of Emery-Dreifuss muscular dystrophy (EDMD), caused by mutations in A-type Lamins (LMNA) and other genes, like Emerin (EMD). We observe that Net39 is downregulated in EDMD patients, implicating Net39 in the pathogenesis of this disorder. Our findings reveal an intimate role for the nuclear envelope in maintaining muscle chromatin organization, gene expression and function, and highlight the importance of Net39 in these processes and in the molecular etiology of EDMD.
2020-11-24 | GSE154849 | GEO
Project description:Lamins and transmembrane proteins within the nuclear envelope are regulators of nuclear structure and chromatin organization. Nuclear Envelope Transmembrane Protein 39 (Net39) is a muscle-restricted nuclear envelope protein. We show that mice lacking Net39 succumb to severe myopathy and neonatal lethality, with concomitant disruption in nuclear integrity, chromatin accessibility, gene expression and metabolism. These abnormalities resemble those of Emery-Dreifuss muscular dystrophy (EDMD), caused by mutations in A-type Lamins (LMNA) and other genes, like Emerin (EMD). We observe that Net39 is downregulated in EDMD patients, implicating Net39 in the pathogenesis of this disorder. Our findings reveal an intimate role for the nuclear envelope in maintaining muscle chromatin organization, gene expression and function, and highlight the importance of Net39 in these processes and in the molecular etiology of EDMD.
2020-11-24 | GSE154848 | GEO
Project description:Lamins and transmembrane proteins within the nuclear envelope are regulators of nuclear structure and chromatin organization. Nuclear Envelope Transmembrane Protein 39 (Net39) is a muscle-restricted nuclear envelope protein. We show that mice lacking Net39 succumb to severe myopathy and neonatal lethality, with concomitant disruption in nuclear integrity, chromatin accessibility, gene expression and metabolism. These abnormalities resemble those of Emery-Dreifuss muscular dystrophy (EDMD), caused by mutations in A-type Lamins (LMNA) and other genes, like Emerin (EMD). We observe that Net39 is downregulated in EDMD patients, implicating Net39 in the pathogenesis of this disorder. Our findings reveal an intimate role for the nuclear envelope in maintaining muscle chromatin organization, gene expression and function, and highlight the importance of Net39 in these processes and in the molecular etiology of EDMD.
2020-11-24 | GSE154847 | GEO