Imaging analysis of six human histone H1 variants reveals universal enrichment of H1.2, H1.3, and H1.5 at the nuclear periphery and nucleolar H1X presence DOI Creative Commons
Mónica Salinas‐Pena, Elena Rebollo, Albert Jordan

et al.

eLife, Journal Year: 2024, Volume and Issue: 12

Published: March 26, 2024

Histone H1 participates in chromatin condensation and regulates nuclear processes. Human somatic cells may contain up to seven histone variants, although their functional heterogeneity is not fully understood. Here, we have profiled the differential distribution of repertoire human through imaging techniques including super-resolution microscopy. variants exhibit characteristic patterns both interphase mitosis. H1.2, H1.3, H1.5 are universally enriched at periphery all cell lines analyzed co-localize with compacted DNA. H1.0 shows a less pronounced peripheral localization, apparent variability among different lines. On other hand, H1.4 H1X distributed throughout nucleus, being high-GC regions abundant nucleoli. Interestingly, show more lacking H1.3 H1.5. The suggest specific functionalities organizing lamina-associated domains or nucleolar activity, which further supported by distinct response phosphorylated inhibition ribosomal DNA transcription. Moreover, depletion affects structure variant-specific manner. Concretely, H1.2 knock-down, either alone combined, triggers global decompaction. Overall, has allowed us distinguish beyond segregation two groups denoted previous ChIP-Seq determinations. Our results support that functionality can be shared between types.

Language: Английский

Role of the cytoskeleton in cellular reprogramming: effects of biophysical and biochemical factors DOI Creative Commons

Ekaterina Momotyuk,

Nour Ebrahim,

Ksenia Shakirova

et al.

Frontiers in Molecular Biosciences, Journal Year: 2025, Volume and Issue: 12

Published: March 7, 2025

The cytoskeleton plays a crucial role in regulating cellular behavior, acting as both structural framework and mediator of mechanical biochemical signals that influence cell fate. In the context reprogramming, modifications to can have profound effects on lineage commitment differentiation efficiency. This review explores impact forces such substrate stiffness, topography, extracellular fluid viscosity, seeding density cytoskeletal organization mechanotransduction pathways, including Rho/ROCK YAP/TAZ signaling. Additionally, we examine agents modulate dynamics, actin microtubule polymerization inhibitors, their stem differentiation. By understanding how remodeling governs identity, this highlights potential strategies for improving reprogramming efficiency directing fate by manipulating cues.

Language: Английский

Citations

0
Nuclear translocation of the LINE-1 encoded ORF1 protein alters nuclear envelope integrity in human neurons DOI Creative Commons

Rania Znaidi,

Olivia Massiani-Beaudoin,

Philippe Mailly

et al.

Brain Research, Journal Year: 2025, Volume and Issue: unknown, P. 149579 - 149579

Published: March 1, 2025

LINE-1 retrotransposons are increasingly implicated in aging and neurodegenerative diseases, yet the precise pathogenic mechanisms remain elusive. While endonuclease reverse transcriptase activities of LINE-1-encoded ORF2p can induce DNA damage inflammation, a role ORF1p cellular dysfunctions stays unassigned. Here we demonstrate, using neuronal model, that translocates into nucleus upon arsenite-induced stress, directly interacting with nuclear import (KPNB1), pore complex (NUP153), lamina (Lamin B1) proteins. Nuclear translocation disrupts integrity, nucleocytoplasmic transport, heterochromatin structure, features linked to neurodegeneration aging. Elevated levels induced either by overexpression, or as observed Parkinson's disease post-mortem brain tissues correlate impaired envelope (NE) morphology. Stress-induced alterations mitigated blocking anti-aging drug remodelin. This study thus reveals action human neurons driving NE thereby contributing LINE-1-mediated cell toxicity.

Language: Английский

Citations

0
The nexus of nuclear envelope dynamics, circular economy and cancer cell pathophysiology DOI Creative Commons
Kristina Keuper, Jiří Bártek, Apolinar Maya‐Mendoza

et al.

European Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 103(2), P. 151394 - 151394

Published: Feb. 6, 2024

The nuclear envelope (NE) is a critical component in maintaining the function and structure of eukaryotic nucleus. NE lamina are disassembled during each cell cycle to enable an open mitosis. Nuclear architecture construction deconstruction prime example circular economy, as it fulfills highly efficient recycling program bound continuous assessment quality functionality building blocks. Alterations dynamics have emerged important contributors both oncogenic transformation cancer progression. However, knowledge breakdown reassembly still limited fraction participating proteins complexes. As cells contain diverse nuclei terms DNA content, but also number, size, shape, great interest understand intricate relationship between these features pathophysiology. In this review, we provide insights into how those regulated, destabilization processes may alter economy. Moreover, expand lamina-associated domain region by using strategic algorithms, including Artificial Intelligence, infer protein associations, assess their location, predict cancer-type specificity with implications for future diagnosis, prognosis treatment. Using approach identified NUP98 MECP2 potential that exhibit upregulation Acute Myeloid Leukemia (LAML) patients early diagnosis.

Language: Английский

Citations

3
NCAPD3 promotes diffuse large B-cell lymphoma progression through modulating SIRT1 expression in an H3K9 monomethylation-dependent manner DOI Creative Commons

Tiange Lu,

Juan Yang, Yiqing Cai

et al.

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: March 1, 2024

Condensin, a family of structural maintenance chromosome complexes, has been shown to regulate compaction and segregation during mitosis. NCAPD3, HEAT-repeat subunit condensin II, plays dominant role in condensin-mediated dynamics but remains unexplored lymphoma. The study aims unravel the molecular function mechanism NCAPD3 diffuse large B-cell lymphoma (DLBCL). expression clinical significance were assessed public database specimens. Chromosome spreads, co-immunoprecipitation (co-IP), mass spectrometry (MS), chromatin immunoprecipitation (ChIP) assays conducted untangle DLBCL. was highly expressed DLBCL, correlated with poor prognosis. deficiency impeded cell proliferation, induced apoptosis increased chemosensitivity. Instead, overexpression facilitated proliferation. In vivo experiments further indicated targeting suppressed tumor growth. Noteworthily, disturbed mitosis, triggering formation aneuploids. To reveal spreads conducted, presenting that chromosomes became compact upon overexpression, instead, loose, twisted lacking axial rigidity absence. Meanwhile, classical transcription-activated marker, H3K4 trimethylation, found globally upregulated after knockout, suggesting might participate remodeling transcription regulation. MS revealed could interact factor, TFII I. Further co-IP ChIP verified be anchored at promoter SIRT1 by I then supported via recognizing H3K9 monomethylation (H3K9me1) on promoter. Function reversion assay oncogenic DLBCL partially mediated SIRT1. This demonstrated dysregulation disturb activity an H3K9me1-dependent manner, which provided novel insights into targeted strategy for

Language: Английский

Citations

3
Imaging analysis of six human histone H1 variants reveals universal enrichment of H1.2, H1.3, and H1.5 at the nuclear periphery and nucleolar H1X presence DOI Creative Commons
Mónica Salinas‐Pena, Elena Rebollo, Albert Jordan

et al.

eLife, Journal Year: 2024, Volume and Issue: 12

Published: March 26, 2024

Histone H1 participates in chromatin condensation and regulates nuclear processes. Human somatic cells may contain up to seven histone variants, although their functional heterogeneity is not fully understood. Here, we have profiled the differential distribution of repertoire human through imaging techniques including super-resolution microscopy. variants exhibit characteristic patterns both interphase mitosis. H1.2, H1.3, H1.5 are universally enriched at periphery all cell lines analyzed co-localize with compacted DNA. H1.0 shows a less pronounced peripheral localization, apparent variability among different lines. On other hand, H1.4 H1X distributed throughout nucleus, being high-GC regions abundant nucleoli. Interestingly, show more lacking H1.3 H1.5. The suggest specific functionalities organizing lamina-associated domains or nucleolar activity, which further supported by distinct response phosphorylated inhibition ribosomal DNA transcription. Moreover, depletion affects structure variant-specific manner. Concretely, H1.2 knock-down, either alone combined, triggers global decompaction. Overall, has allowed us distinguish beyond segregation two groups denoted previous ChIP-Seq determinations. Our results support that functionality can be shared between types.

Language: Английский

Citations

3