Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Nuclear organization”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2025

Dynamic changes in chromosome and nuclear architecture during maturation of normal and ALS C9orf72 motor neurons.

We have investigated changes in chromosome conformation, nuclear organization, and transcription during differentiation and maturation of control and mutant motor neurons harboring hexanucleotide expansions in the C9orf72 gene that cause amyotrophic lateral sclerosis (ALS). Using an in vitro reprogramming, differentiation and neural maturation protocol, we obtained highly purified populations of post-mitotic motor neurons for both normal and diseased cells. As expected, as fibroblasts are reprogrammed into iPSCs, and as iPSCs differentiate into motor neurons, chromatin accessibility, chromosome conformation, and nuclear organization change along with large-scale alterations in transcriptional profiles. We find that the transcriptome changes extensively during the first three weeks of post-mitotic neuronal maturation, with thousands of genes changing expression, but then is relatively stable for the next three weeks. In contrast, chromosome conformation and nuclear organization continue to change over the entire 6-week maturation period: chromosome territoriality increases, long-range interactions along chromosomes decrease, compartmentalization strength increases, and centromeres and telomeres increasingly cluster. In motor neurons derived from ALS patients such changes in chromosome conformation were much reduced. Chromatin accessibility changes also showed delayed maturation. The transcriptome in these cells matured relatively normally but with notable changes in expression of genes involved in lipid, sterol and mitochondrial function. We conclude that neural maturation is associated with large scale post-mitotic changes in gene expression, chromosome conformation and nuclear organization, and that these processes are defective in motor neurons derived from ALS patients carrying C9orf72 hexanucleotide repeat expansions.

Journal Article↗
PubMed2025

Differential Crosslinking and Contractile Motors Drive Nuclear Chromatin Compaction.

During interphase, a typical cell nucleus features spatial compartmentalization of transcriptionally active euchromatin and repressed heterochromatin domains. In conventional nuclear organization, euchromatin predominantly occupies the nuclear interior, while heterochromatin, which is approximately 50% more dense than euchromatin, is positioned near the nuclear periphery. Peripheral chromatin organization can be further modulated by the nuclear lamina, which is itself a deformable structure. While a number of biophysical mechanisms for compartmentalization within rigid nuclei have been explored, we study a chromatin model consisting of an active, crosslinked polymer tethered to a deformable, polymeric lamina shell. Contractile motors, the deformability of the shell, and the spatial distribution of crosslinks all play pivotal roles in this compartmentalization. We find that a radial crosslink density distribution, even with a small linear differential of higher crosslinking density at the edge of the nucleus, combined with contractile motor activity, drives genomic segregation, in agreement with experimental observations. This arises from contractile motors preferentially drawing crosslinks into their vicinity at the nuclear periphery, forming high-density domains that promote heterochromatin formation. We also find an increased stiffness of nuclear wrinkles given the preferential heterochromatin compaction below the lamina shell, which is consistent with instantaneous nuclear stiffening under applied nanoindentation. We conclude with the potential for experimental validation of our model predictions.

Journal Article↗
PubMed2025

Differential Crosslinking and Contractile Motors Drive Nuclear Chromatin Compaction.

During interphase, a typical cell nucleus features spatial compartmentalization of transcriptionally active euchromatin and repressed heterochromatin domains. In conventional nuclear organization, euchromatin predominantly occupies the nuclear interior, while heterochromatin, which is approximately 50% more dense than euchromatin, is positioned near the nuclear periphery. Peripheral chromatin organization can be further modulated by the nuclear lamina, which is itself a deformable structure. While a number of biophysical mechanisms for compartmentalization within rigid nuclei have been explored, we study a chromatin model consisting of an active, crosslinked polymer tethered to a deformable, polymeric lamina shell. Contractile motors, the deformability of the shell, and the spatial distribution of crosslinks all play pivotal roles in this compartmentalization. We find that a radial crosslink density distribution, even with a small linear differential of higher crosslinking density at the edge of the nucleus, combined with contractile motor activity, drives genomic segregation, in agreement with experimental observations. This arises from contractile motors preferentially drawing crosslinks into their vicinity at the nuclear periphery, forming high-density domains that promote heterochromatin formation. We also find an increased stiffness of nuclear wrinkles given the preferential heterochromatin compaction below the lamina shell, which is consistent with instantaneous nuclear stiffening under applied nanoindentation. We conclude with the potential for experimental validation of our model predictions.

Journal Article↗
PubMed2026

The TUBG meshwork is associated with centromere dynamics and micronuclear organization.

This study investigates how γ-tubulin and the centrosome contribute to interphase centromere dynamics and nuclear organization. Although classically associated with mitotic microtubule nucleation, here we show that γ-tubulin associates with chromatin and is enriched within centromere-defined volumes. Using live-cell imaging, immunofluorescence, and chromatin immunoprecipitation sequencing, we detect γ-tubulin-associated signal at satellite-rich, centromere-proximal chromatin. Reduced γ-tubulin levels are associated with increased centromere fluorescence intensity and reduced mobility, linking the γ-tubulin network to centromere organization. Under acute cisplatin-induced stress, centromere mobility increases, whereas centromere clustering is observed in separate fixed-cell analyses. Ser131 phosphorylation is associated with γ-tubulin self-assembly and centromere-related dynamics. Additionally, γ-tubulin accumulates in micronuclei, coinciding with increased replication-associated signal and DNA fluorescence. In primary clear cell renal cell carcinoma cells, stress is associated with higher γ-tubulin fluorescence intensity within centromere-defined volumes. Together, these findings support an association between the γ-tubulin meshwork and centromere organization, chromatin compartmentalization, and responses to genomic stress.

Centromere↗
PubMed2025

An Optimized Adaptation of DamID for NGS Applications.

Recent studies have implicated higher-order genome organization in the regulation of genes and cellular state. Lamina-Associated Domains (LADs) are regions of heterochromatin associated with the nuclear envelope and the nuclear lamina, a protein network involved in both nuclear organization and genome structure. LADs are developmentally regulated, and their dysregulation is associated with several diseases and pathological states, including cancer and premature aging. In addition to LADs, other nuclear protein compartments appear to scaffold or support unique chromatin environments to affect gene expression. These revelations carry profound implications for our comprehension of developmental processes and the pathogenesis of various diseases, especially given the numerous disorders already directly associated with, for example, mutations in lamin and INM proteins. This spatial compartmentalization of chromatin subtypes to unique protein compartments has led to the adoption of proximity-labeling methods, such as DamID (DNA Adenine Methyltransferase Identification), to identify these unique chromatin compartments.

Humans↗
PubMed2025

Extrinsic heterogeneity: Collectivity in isotropic conformational fluctuations of chromosomes.

Eukaryotic interphase chromosomes maintain a three-dimensional conformation within the nucleus and undergo fluctuations. However, the analysis of chromosome conformational fluctuations has been mainly limited to chromosome conformation capture data that record the contact frequencies between chromosomal regions. Herein, we investigated chromosome fluctuations as polymers based on experimental data from sequential fluorescence in situ hybridization using a multiomics methodology. To describe the principal modes of chromosome fluctuations, we applied principal-component analysis to the three-dimensional conformation information of single chromosomes in 446 mouse embryonic stem cells obtained from sequential fluorescence in situ hybridization data analysis for spatial genomics and signals of nuclear factors (histone marks, repeat DNAs, and proteins in interchromosomal nuclear compartments). We found that chromosome fluctuations exhibit both isotropic and anisotropic modes. The isotropic conformational fluctuations of all chromosome types tended to synchronize each other, reflecting extrinsic heterogeneity in chromosome conformation that is independent of the cell cycle. In contrast, anisotropic conformational fluctuations, occurring in a spindle-like shape, were associated with the interactions between repeat DNAs and nuclear factors. These results highlight the importance of dissecting cell-cycle-independent nuclear organization based on the conformational folding of chromosomes and the interactions between genomic regions and nuclear factors.

Animals↗
PubMed1978

The organization, composition and matrix of hepatocyte nuclei exposed to alpha-amanitin.

Alterations in the structure and molecular composition of avian hepatocyte nuclei were compared following administration in vivo of lethal and sub-lethal doses of alpha-amanitin. This toxin interferes with extranucleolar transcription by direct inhibition of RNA polymerase II activity. the resultant effects include: extensive condensation of chromatin, displacement of nucleoplasmic contents and fragmentation of nucleoli. Changes in nuclear morphology were quantitated by stereometry and related to variations in RNA and residual, non-histone proteins (NHP). Gross alterations in nuclear structure and depletion of RNA and NHP levels were of similar magnitude with both doses of amanitin. The effects were fully reversible, however, with a minimal dose but terminal with a lethal dose. DNA and histone protein levels remained unchanged at all stages. These results imply that the process of transciption may itself keep and/or maintain chromatin in a dispersed state, and that in the absence of transcription chromatin naturally condenses. Modification of nuclear proteins may be necessary only to maintain chromatin compacted permanently or for extended periods of time. A model of nuclear organization is proposed to incorporate these considerations and to identify the probable location of the nuclear matrix in situ.

Amanitins↗
PubMedDate not supplied

[Influence of dibutyryl cyclic AMP and theophylline on the frequency of nuclear microtubules and microfilaments of sympathetic neurons].

In vivo dibutyryl cyclic AMP and theophylline, as does electrical stimulation, increase the frequency of nuclear microtubules and microfilaments in neurons of cat stellate ganglia. These and previous results lead us to conclude that cyclic AMP mediates the process of assembly of these two structural components from preformed protein subunits and thus triggers the formation of highly organized nuclear inclusions corresponding to the so-called intranuclear rodlets of light microscopy.

Animals↗
PubMed2026

Mediator at the Helm: Coordinating transcription and biomolecular condensates in hematopoiesis.

Hematopoiesis relies on precisely coordinated transcriptional programs that balance stem cell self-renewal, lineage commitment, and terminal differentiation. Central to this regulation is the Mediator complex, a large multi-subunit transcriptional co-regulator that integrates signals from transcription factors and chromatin regulators to control RNA polymerase Ⅱ (Pol Ⅱ) activity. The dynamic and modular composition of Mediator enables context-dependent transcriptional outputs, while individual subunits can exert specialized regulatory functions during hematopoietic lineage specification, thereby contributing to cell-fate-specific transcriptional outputs. Recent advances further reveal that transcriptional regulation is shaped by the spatial organization of regulatory machinery with biomolecular condensates formed through liquid-liquid phase separation (LLPS), particularly at super-enhancers. In this emerging framework, Mediator functions not only as a transcriptional integrator but also as a key coordinator of transcriptional machinery within condensates at cell-fate-related gene loci. In this chapter, we summarize how distinct Mediator subunits confer specific modes of transcriptional regulation and discuss how the interplay between Mediator and phase-separated condensates shapes transcriptional control during hematopoiesis. We highlight how specific subunits, including MED1 and MED26, participate in distinct regulatory modes in erythropoiesis, spanning super-enhancer-driven transcriptional activation, progenitor expansion, and condensate-associated mechanisms that influence Pol Ⅱ pausing and global transcription repression during terminal differentiation. Together, these findings support a model in which Mediator integrates transcriptional regulation with nuclear organization through condensate-mediated mechanisms, providing a conceptual framework for understanding hematopoietic cell fate decisions and transcriptional dysregulation in hematological diseases.

Hematopoiesis↗
PubMed1978

An ultrastructural study of the sporogonic development of Plasmodium falciparum in Anopheles gambiae.

This paper describes the fine structure of the sporogonic development of Plasmodium falciparum in its natural vector Anopheles gambiae (Species A) as seen by scanning and transmission electron microscopy. The parasite was derived from naturally infected volunteers and the vector maintained under natural conditions at the MRC Laboratories, Fajara, The Gambia. Sporogonic development of P. falciparum is similar to that described for other Plasmodium spp. There are however greater similarities between P. falciparum and the avian malaria parasites, than those mammalian (primarily rodent) species described to date--particularly with respect to mitochondrial development, crystalloid morphology and nucleolar organization. Nuclear development is similar to that of the murine malaria parasites, but reconstruction of complete mitotic spindles from serial sections suggest the haploid genome of P. falciparum contains 14 chromosomes compared to eight to ten in the murine plasmodia. Sporoblast formation involves a unique process of cleft formation based on the expansion of the cisternal space of the endoplasmic reticulum. Sporozoite budding is almost exclusively confined to these inner membrane surfaces and results in a characteristic sporozoite distribution in the oocyst. High resolution scanning electron microscopy of free sporozoites provides the first surface view of the micropore of Plasmodium.

Anopheles↗
PubMed1979

Detection of substance P in the central nervous system by a monoclonal antibody.

Peptides with transmitter-like characteristics are being found in many brain areas. The application of immunocytochemical and radioimmunoassay methods has contributed much to the clarification of these neuronal systems. Here we report the development of a rat monoclonal antibody produced by a hybrid myeloma and its application to the study of one of these peptides, substance P. The hybrid clone, isolated after fusion of mouse myeloma cells with hyperimmune rat spleen cells, allowed us to obtain a standardized and permanent source of monoclonal substance P antibodies in a culture cell system. This antibody recognizes the COOH-terminal part of substance P in radioimmunoassay down to 10-20 fmol. It does not crossreact with other known mammalian brain peptides tested. By immunofluorescence the antibody was shown to bind specifically and with a remarkably low background to nerve terminals and cell bodies located in clearly defined nuclear organizations of the central nervous system.

Animals↗
PubMed2026

Enhanced chromatin compaction is associated with de novo expression of a nuclear microprotein, global loss of H3 acetylation and local transcriptional changes in retinal rod photoreceptors.

We have limited understanding of how aging alters gene expression and remodels cellular architecture in post-mitotic neurons. The inverted nuclear organization of mouse rod photoreceptors provides a unique model to gain mechanistic insights into age-associated decline in neuronal function. We have generated and integrated multi-omic datasets including 3D-genome topology, histone modifications, chromatin accessibility, DNA methylation and transcriptome of rod photoreceptors from young- and aged-mice. We show that aging drives global chromatin compaction, with regional alterations enriched at active chromatin. Epigenomic and transcriptional changes broadly correlate with chromatin dynamics as validated by high resolution microscopy. We uncover a megabase-sized genomic region with multi-level alterations, including de novo transcription of Gm7239, which encodes a functional microprotein carrying histone acetyltransferase-inhibitor domain. Overexpression of Gm7239 is associated with global loss of histone H3 acetylation, highlighting a potential new axis of genomic regulation in aging. Finally, we identify multiple significant local transcriptional alterations in non-annotated regions and genes associated with age-related macular degeneration. Our studies link age-related chromatin landscape changes with gene expression that may influence rod function and vulnerability to diseases.

Journal Article↗
PubMed1979

The organization of a nuclear DNA sequence from a higher plant: molecular cloning and characterization of soybean ribosomal DNA.

The recombinant DNA vector, lambda Charon 4A, was used to construct a library of DNA sequences from the genomic DNA of soybean (Glycine max). To define the organization of ribosomal DNA (rDNA) in the soybean genome, clones containing sequences complementary to both 17S and 25S rRNA have been isolated from this library and used in conjunction with Southern blot hybridization. The rRNA genes are tandemly reiterated with a relatively small unit repeat length of 7.8 kb. There is no heterogeneity in the length of the rDNA repeat units although they display limited differences in either base sequence or pattern of methylation. The cloned rDNA sequences are shown to comprise the entire repeat unit and have been used to obtain a detailed restriction map as well as an approximate transcription map of soybean rRNA genes. The cloning of rDNA from soybean suggests that recombinant DNA techniques can be successfully applied to the genomic DNA of higher plants despite the high degree of methylation exhibited by plant DNA.

Bacteriophage lambda↗
PubMed1977

Studies on sex-organ development. Changes in nuclear and chromatin composition and genomic activity during spermatogenesis in the maturing rooster testis.

We developed a technique to separate nuclei of rooster testis by centrifugation through a discontinuous sucrose density gradient and by sedimentation at unit gravity. Four different major fractions obtained from testicular nuclei and one from the vas deferens were characterized according to their velocity of sedimentation, morphology and DNA content. The ratios (w/w) of basic proteins, non-histone proteins and RNA to DNA decreased during spermiogenesis both in nuclei and chromatin. Changes in the electrophoretic patterns of histones and non-histone proteins were detected especially in the elongated spermatids. The lack of uptake of [3H]uridine in elongating and elongated spermatids and in spermatozoa was demonstrated by radioautography and by the detection of labelled RNA extracted from different fractions of nuclei. Template activity for RNA synthesis and the binding of actinomycin D by testicular nuclei reached a peak in the elongated spermatid stage, when the histones are replaced by the protamine.

Animals↗
PubMed2026

ATRX Condensates as Candidate Organizers of Enhancer-Centered Nuclear Microenvironments in Neural Progenitors: A Hypothesis for Enhancer-Associated ATRX Function in Neural Progenitors.

Neural progenitor cells (NPCs) must preserve lineage identity while remaining responsive to developmental cues. Here, we discuss the hypothesis that ATRX condensates help organize enhancer-centered nuclear microenvironments in NPCs. ATRX has long been studied in heterochromatin maintenance, histone variant deposition, and chromatin remodeling; earlier work has also shown that ATRX can occupy euchromatic and active regulatory regions and contribute to transcriptional regulation. Recent evidence in human NPCs indicates that ATRX forms nuclear puncta with condensate-like properties, associates with neurogenic enhancer-rich regions, and incorporates regulatory factors such as CHD7 and p300. Perturbation of ATRX condensate formation is associated with changes in enhancer-associated ATRX occupancy, neural gene-expression programs, and neuroepithelial organization, suggesting a regulatory mode that may complement canonical heterochromatin-associated functions. We propose a dual-mode model in which folded domains contribute to chromatin anchoring at repressive regions, whereas intrinsically disordered regions support condensate-associated organization at active developmental enhancers. We emphasize that whether ATRX condensates activate enhancers de novo, stabilize pre-existing enhancer states, buffer transcriptional variability, or primarily organize cofactor localization remains unresolved. We also discuss limitations of the current evidence and outline acute, locus-specific experiments needed to test the model.

X-linked Nuclear Protein↗
PubMed1979

The inability of nuclear dehydrogenating clostridia to oxidize bile salt hydroxyl groups.

In a survey of the intracellular bile salt oxidoreductase activity in fecal bacteria, 16 strains of nuclear dehydrogenating clostridia and 2 strains of non-nuclear dehydrogenating C. paraputrificum were demonstrated unable to oxidize cholate at any of the 3 OH groups. Since nuclear dehydrogenation at the delta-1 and delta-4 position requires a 3-oxo precursor steroid, it appears that these organisms require the presence of a 3 alpha-hydroxysteroid dehydrogenating organism for nuclear dehydrogenation.

Bile Acids and Salts↗