Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Nuclear Matrix”

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 1,495 records · Page 83Linked to original sources
PubMed1989

Binding of polycyclic and nitropolycyclic aromatic hydrocarbons to specific fractions of rat lung chromatin.

Carcinogen-induced damage to nuclear matrix DNA, the site of DNA replication and transcription, could have profound effects on gene regulation and mutation. 1,6-Dinitropyrene (1,6-DNP), 1-nitropyrene (1-NP), 6-nitrobenzo[a]pyrene (6-NBP), benzo[a]pyrene (BP) and benzo[a]pyrene diolepoxide (BPDE) were investigated for their abilities to bind to selected regions of DNA in rat lung cell nuclei. Following in vitro exposure to carcinogen, nuclei were fractionated into active chromatin (AC), nuclear matrix (NM) and bulk (low and high salt) chromatin fractions. At an equivalent molar concentration, the highest binding to unfractionated (total) DNA was obtained with BPDE, followed in order by BP, 1,6-DNP, 6-NBP and 1-NP. BPDE, a direct alkylating compound, was bound approximately 18 times higher than the other compounds. All compounds were bound to AC (mononucleosomal DNA approximately 185 bp) and to NM in greater amounts than to bulk DNA. The binding ratios (AC + NM)/(LS + HS) varied from 2 to 21, depending upon the compound. The selective binding to specific DNA regions did not appear to be significantly related to the structures of the parent compounds or to their inferred metabolites. Thus, it appears that selective binding to specific regions is a general phenomenon that is related to the open state of the chromatin structure.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1984

A monoclonal antibody recognizes an epitope common to an avian-specific nuclear antigen and to cytokeratins.

X3, a monoclonal antibody of unusual specificity, is described. This antibody reacts with one or more cytokeratin polypeptides and also reacts with an avian (chicken, quail) nuclear antigen that appears to be present in all cell types (chicken) tested, although with variable staining pattern and intensity. This antigen is distinct from the cytokeratins but does have an epitope in common with this class of proteins. It disappears from the nucleus during the early stages of cell division and reappears during anaphase as a granular cytoplasmic structure. In late telophase the antigen is relocated in the nucleus. This antigen, which we have designated as avian-specific nuclear antigen ( AVNA ), is not associated with chromatin or ribonucleoproteins. From immunoblotting experiments on chicken fibroblast nuclei, AVNA is probably a complex composed of one or several polypeptides, one of which has a molecular weight of approximately 60 kD. The proteins were identified as nuclear matrix proteins rather than pore complex-lamina proteins by immunoblotting experiments on the purified nuclear matrix of chicken erythrocytes. The major polypeptide had a molecular weight of 60 kD and the minor polypeptide a molecular weight of 69 kD.

Animals↗
PubMed1995

Modular structural elements in the replication origin region of Tetrahymena rDNA.

Computer analyses of the DNA replication origin region in the amplified rRNA genes of Tetrahymena thermophila identified a potential initiation zone in the 5'NTS [Dobbs, Shaiu and Benbow (1994), Nucleic Acids Res. 22, 2479-2489]. This region consists of a putative DNA unwinding element (DUE) aligned with predicted bent DNA segments, nuclear matrix or scaffold associated region (MAR/SAR) consensus sequences, and other common modular sequence elements previously shown to be clustered in eukaryotic chromosomal origin regions. In this study, two mung bean nuclease-hypersensitive sites in super-coiled plasmid DNA were localized within the major DUE-like element predicted by thermodynamic analyses. Three restriction fragments of the 5'NTS region predicted to contain bent DNA segments exhibited anomalous migration characteristic of bent DNA during electrophoresis on polyacrylamide gels. Restriction fragments containing the 5'NTS region bound Tetrahymena nuclear matrices in an in vitro binding assay, consistent with an association of the replication origin region with the nuclear matrix in vivo. The direct demonstration in a protozoan origin region of elements previously identified in Drosophila, chick and mammalian origin regions suggests that clusters of modular structural elements may be a conserved feature of eukaryotic chromosomal origins of replication.

Animals↗
PubMed1985

Nuclear protein, matrix and structural changes in rooster liver after estrogenic induction of vitellogenesis.

The estrogenic induction of vitellogenesis in avian and amphibian liver has been well characterized at the target gene level. Comparatively little however, is known about cognate nuclear events associated with the response, particularly those involving large-scale structural changes and the non-histone proteins (NHP). We have examined these aspects further in primary stimulated roosters. In the first 24 hr post induction with estradiol, hepatocyte nuclei enlarged by 50% and exhibited sharp rises in total protein and RNA content. In particular, the mass of residual NHP rose about 40%. Extensive internal reorganization was evident, including partial disaggregation of chromatin, proliferation of interchromatin components and de novo appearance of prominent "nuclear bodies". These changes were accompanied by quantitative fluctuations in nucleoplasmic and several matrix fraction proteins. A marked relative decrease was evident in all three lamins, as well as approximately 75 and approximately 175 kD proteins. Hn-RNP-associated polypeptides however, and various unidentified components became much more prominent. By 24 hr, cells were fully differentiated for bulk export of vitellogenin and low density lipoproteins. All changes persisted for several days before gradually regressing to normal over a 2-4 week period. Many key nuclear modifications, however, did not regress fully, including persistent enlargement, elevated NHP content and modified matrix fraction proteins. Collectively, these may reflect part of the "memory" effect, commonly observed in steroid target tissues, whereby a second, more pronounced response can be triggered long after primary induction has subsided.

Animals↗
PubMed1988

Chromosomal loop/nuclear matrix organization of transcriptionally active and inactive RNA polymerases in HeLa nuclei.

The relative distribution of transcriptionally active and inactive RNA polymerases I and II between the nuclear matrix/scaffold and chromosomal loops of HeLa cells was determined. Total RNA polymerase was assessed by immunoblotting and transcribing RNA polymerase by a photoaffinity labeling technique in isolated nuclei. Nuclear matrix/scaffold was isolated by three methods using high-salt, intermediate-salt or low-salt extraction. The distribution of RNA polymerases I and II were very similar within each of the methods, but considerable differences in distributions were found between the different preparation methods. Either intermediate-salt or high-salt treatment of DNase I-digested nuclei showed significant association of RNA polymerases with the nuclear matrix. However, intermediate-salt followed by high-salt treatment released all transcribing and non-transcribing RNA polymerases. Nuclear scaffolds isolated with lithium diiodosalicylate (low-salt) contained very little of the RNA polymerases. This treatment, however, caused the dissociation of RNA polymerase II transcription complexes. These results show unambiguously that RNA polymerases, both in their active and inactive forms, are not nuclear matrix proteins. The data support models in which the transcriptional machinery moves around DNA loops during transcription.

Affinity Labels↗
PubMed2000

Inactivation of 14-3-3sigma influences telomere behavior and ionizing radiation-induced chromosomal instability.

Telomeres are complexes of repetitive DNA sequences and proteins constituting the ends of linear eukaryotic chromosomes. While these structures are thought to be associated with the nuclear matrix, they appear to be released from this matrix at the time when the cells exit from G(2) and enter M phase. Checkpoints maintain the order and fidelity of the eukaryotic cell cycle, and defects in checkpoints contribute to genetic instability and cancer. The 14-3-3sigma gene has been reported to be a checkpoint control gene, since it promotes G(2) arrest following DNA damage. Here we demonstrate that inactivation of this gene influences genome integrity and cell survival. Analyses of chromosomes at metaphase showed frequent losses of telomeric repeat sequences, enhanced frequencies of chromosome end-to-end associations, and terminal nonreciprocal translocations in 14-3-3sigma(-/-) cells. These phenotypes correlated with a reduction in the amount of G-strand overhangs at the telomeres and an altered nuclear matrix association of telomeres in these cells. Since the p53-mediated G(1) checkpoint is operative in these cells, the chromosomal aberrations observed occurred preferentially in G(2) after irradiation with gamma rays, corroborating the role of the 14-3-3sigma protein in G(2)/M progression. The results also indicate that even in untreated cycling cells, occasional chromosomal breaks or telomere-telomere fusions trigger a G(2) checkpoint arrest followed by repair of these aberrant chromosome structures before entering M phase. Since 14-3-3sigma(-/-) cells are defective in maintaining G(2) arrest, they enter M phase without repair of the aberrant chromosome structures and undergo cell death during mitosis. Thus, our studies provide evidence for the correlation among a dysfunctional G(2)/M checkpoint control, genomic instability, and loss of telomeres in mammalian cells.

14-3-3 Proteins↗
PubMed2002

Urine: beyond cytology for detection of malignancy.

In the present review we discuss various ancillary modalities for detection of malignancies in urine samples, with an emphasis on urothelial carcinomas. Flow cytometry, bladder tumor antigen (BTA), nuclear matrix protein (NMP), matrix metalloproteinase (MMP), human chorionic gonadotrophic (HCG), telomerase, and other techniques are discussed. DNA FCM is a relatively costly and sophisticated technique. It has a practical application in the diagnosis of bladder cancer among subjects at high risk and is of value in monitoring the course of the disease and anticipating recurrence following conservative treatment. The BTA test is a simple, rapid, and inexpensive adjunct to cystoscopy and the results of the test are equivalent or superior to those of voided urinary cytology. NMP-22 immunoassay is a useful diagnostic test for predicting recurrence of urothelial malignancy. It is also a cost-effective and sensitive screening test for detecting tumor in patients with urothelial carcinoma. Beta-HCG estimation in urine samples appears to be an efficient diagnostic marker for the assessment of distant metastasis in bladder carcinoma rather than a screening test. Other ancillary techniques such as detection of expression of cytokeratin 20 by RT-PCR, MMP-9 estimation, and fluorescent in situ hybridization and telomerase activity are rarely applied clinically in routine urinary samples and are not cost-effective.

Antigens, Neoplasm↗
PubMed1983

Distribution of interchromatin granules in nuclear matrices obtained from nuclei exhibiting different degree of chromatin condensation.

Female Wistar rats were injected intraperitoneally with thioacetamide or Ledakrin (1-nitro-9/3'-dimethylpropyloamine/acridine . 2 HCl) to provoke chromatin decondensation or condensation, respectively. Liver nuclei of each experimental group were used to isolate nuclear matrices. The results provide evidence that interchromatin granules are components of the nuclear matrix obtained by the procedure used in these experiments. They also reveal that the general ultrastructural pattern of the nuclear matrix is related to the degree of chromatin condensation in the nuclei used for its isolation. The distribution of interchromatin granules characteristic for the source nuclei is maintained in the nuclear matrices.

Animals↗
PubMed2002

Osteoblast intracellular localization of Nmp4 proteins.

Nmp4 proteins are transcription factors that contribute to the expression of type I collagen and many of the matrix metalloproteinase genes. Numerous Nmp4 isoforms have been identified. These proteins, all derived from a single gene, have from five to eight Cys(2)His(2) zinc fingers, the arrangement of which directs specific isoforms to nuclear matrix subdomains. Nmp4 isoforms also have an SH3 binding domain, typical of cytoplasmic docking proteins. Although recent evidence indicates that Nmp4 proteins also reside in the osteoblast cytoplasm, whether they localize to specific organelles or structures is not well defined. The intracellular localization of a protein is a determinant of its function and provides insights into its mechanism of action. As a first step toward determining the functional relationship between the cytoplasmic and nuclear Nmp4 compartments, we mapped their location in the osteoblast cytoplasm. Immunocytochemical analysis of osteoblasts demonstrated that Nmp4 antibodies labeled the mitochondria, colocalized with Golgi protein 58K, and lightly stained the cytoplasm. Western analysis using Nmp4 antibodies revealed a complex profile of protein bands in the nuclear, mitochondrial, and cytosolic fractions. Several of these proteins were specific to defined intracellular domains. Consistent with the western analyses, reverse transcription-polymerase chain reaction (RT-PCR) analysis detected previously uncharacterized Nmp4 isoforms. These data necessarily enlarge the known Nmp4 family from nuclear matrix transcription factors to a more widely extended class of intracellular proteins.

3T3 Cells↗
PubMedDate not supplied

Association of EGFR gene fragments with nuclear matrices in glioblastoma cell lines.

The association of epidermal growth factor receptor DNA fragments with nuclear matrix in glioblastoma cell lines was investigated. Two different DNA fragments (primer I-III, 940 bp and primer IV-V, 110 bp) were amplified in both genomic DNA and nuclear matrix-associated DNA. It was found that the 110 bp DNA fragment (primer IV-V) from a non-encoding region was more closely associated with the nuclear matrices of cell line U343, U373, A172, and T98 than with U87. The other DNA fragment (primer I-III) was found in both the genomic DNA and NM DNA from cell line of U343 and U87. Another long DNA fragment (primer I-II, 1015 bp) was not detected in the DNA of all cell lines. Our findings suggest that the attachment of the 110 bp DNA fragments to nuclear matrix may contribute to the growth and malignancy of glioblastoma.

DNA Fragmentation↗
PubMed2004

Genetic alterations of the NRP/B gene are associated with human brain tumors.

Nearly all brain tumors develop following the progressive accumulation of genetic alterations of oncogenes and tumor suppressor genes (such as p53 and retinoblastoma protein). Furthermore, aberrations in the nuclear matrix often contribute to genomic instabilities and the development of cancer. We have previously shown that nuclear-restricted protein/brain (NRP/B), a member of the BTB/Kelch repeat family, is a nuclear matrix protein normally expressed in neurons but not in astrocytes, and that it is an early and specific marker of neurons during the development of the central nervous system. Here, we show aberrant expression of NRP/B in human brain tissues. NRP/B is expressed in the cytoplasm of human brain tumor cells (glioblastoma, GBM) arising from astrocytes. NRP/B mutations (13 mutations in the Kelch domains, two in the intervening sequence (IVS) domain and two in the BTB domain) were detected in brain tumor cell lines (A-172, CCF-STTG1, SK-N-SH and U87-MG) and in primary human malignant GBM tissues (eight samples). More importantly, we found that NRP/B mutants, but not wild-type (wt) NRP/B, increased the activation of ERK and consequently promoted cell proliferation, attenuated caspase activation and suppressed the cellular apoptosis induced by the stressful stimulus cisplatin (10 microM). These events were observed to occur via a p53-mediated pathway. In addition, while wt NRP/B was associated with actin, mutations in the Kelch domains of NRP/B led to its reduced binding affinity to actin. Thus, alterations and gene mutations within the NRP/B gene may contribute to brain tumorigenesis by promoting cell proliferation, suppressing apoptosis and by affecting nuclear cytoskeleton dynamics.

Amino Acid Motifs↗
PubMedDate not supplied

[The spatial organization of DNA in the nucleus may determine positions of recombination hot-spots].

We suggest a hypothesis postulating that sites of DNA loop anchorage to the nuclear matrix harbor "hot spots" of illegitimate recombination which is mediated or triggered by topoisomerase II of the nuclear matrix. Recombination between DNA loop anchorage sites may result in deletion and/or repositioning of DNA loops and loop oligomers. This hypothesis is corroborated by our own results and published results of other research groups.

Cell Nucleus↗
PubMed1993

Isolation of matrices from maize leaf nuclei: identification of a matrix-binding site adjacent to the Adh1 gene.

Nuclear matrices were isolated from maize leaves by the two conventional methods usually employed for the preparation of the corresponding structures of animal origin. It is demonstrated that functionally competent matrices, recognizing and specifically binding the MAR-containing DNA of the mouse kappa-immunoglobulin gene may be prepared by both 2 M NaCl and LIS extractions of maize nuclei. A DNA region with a high affinity for the nuclear matrix was identified at the 5' end of the maize Adh1-S gene, distal to the promoter region. The presence of sites of reported altered chromatin structure in this particular region is discussed. While the proximity and the cohabitation of MARs with different regulatory elements is a common feature of matrix association regions in animal systems, this is the first plant MAR identified in a region of known significance for gene regulation.

Alcohol Dehydrogenase↗
PubMed2006

Completing the cycles; the dynamics of endonuclear lipidomics.

Signal transductions via periodic generation and mobilisation of lipid second messengers within the nuclear matrix of eukaryotic cells have focused renewed attention on their precursor phospholipids' location, structure, form and function. The nuclear matrix contains and supports dynamic pools of phosphatidylcholine and phosphatidylinositol which serve as parent molecules of lipid second messengers but also of other phospholipids requiring cyclical replacement as cells proliferate. Applications of new, highly sensitive and specific analytical methodologies based on tandem electrospray ionisation mass spectrometry and the use of stable isotopes have allowed both static and dynamic lipidomic profiling of these endonuclear phospholipid pools. Together with more conventional enzymatic analyses and evaluation of the effect of specific "knock-out" of phospholipid transfer capacity, a number of important principles have been established. Specifically, a compartmental capacity to synthesise and remodel highly saturated phosphatidylcholine exists alongside transport mechanisms that facilitate the nuclear import of phosphatidylinositol and other phospholipids synthesised elsewhere within the cell. Subnuclear fractionation and the use of newly emerging techniques for sensitive lipidomic profiling of polyphosphoinositides, diacylglycerols and phosphatidate molecular species offer the potential for further significant advances in the near future.

Animals↗
PubMed2004

Poly(ADP-ribose) polymerase-1: association with nuclear lamins in rodent liver cells.

The distribution of poly(ADP-ribose) polymerase-1 (PARP-1) over different nuclear compartments was studied by nuclear fractionation procedures and Western analysis revealing a prominent role of the nuclear matrix. This structure is operationally defined by the solubility properties of the A- and B-type lamins under defined experimental conditions. We consistently observed that most of the nuclear matrix-associated PARP-1 partitioned, in an active form, with the insoluble, lamin-enriched protein fractions that were prepared by a variety of established biochemical procedures. These PARP-1-protein interactions resisted salt extraction, disulfide reduction, RNase and DNase digestion. An inherent ability of PARP-1 to reassemble with the lamins became evident after a cycle of solubilization/dialysis using either urea or Triton X-100 and disulfide reduction, indicating that these interactions were dominated by hydrophobic forces. Together with in vivo crosslinking and co-immunoprecipitation experiments our results show that the lamins are prominent PARP-1-binding partners which could contribute to the functional sequestration of the enzyme on the nuclear matrix.

Animals↗
PubMed2000

Clinical usefulness of the novel marker BLCA-4 for the detection of bladder cancer.

PURPOSE: Previous studies at our laboratory identified 6 bladder cancer specific nuclear matrix proteins termed BLCA-1 to 6. We recently developed an immunoassay that detects the bladder cancer specific nuclear matrix protein BLCA-4. We analyzed urine samples from patients with bladder cancer, those with spinal cord injury and normal volunteers to determine the BLCA-4 level in these 3 groups. MATERIALS AND METHODS: Urine samples obtained from 51 normal controls, and 54 patients with bladder cancer and 202 with spinal cord injury were tested for BLCA-4. We evaluated the association of BLCA-4 level with tumor grade and stage, urine cytology and bladder cancer history in the nonspinal cord injured population. Similarly we compared parameters associated with BLCA-4, such as spinal cord injury duration, catheterization, history of urinary tract infection, smoking and urine culture, in spinal cord injured patients. RESULTS: We established a normal cutoff point of 13 optical density units per microg. protein for the BLCA-4 assay. The BLCA-4 level was less than the cutoff in all 51 normal controls, while in 53 of the 55 urine samples (96.4%) of patients with bladder cancer and 38 of the 202 (19%) of spinal cord injured patients urinary BLCA-4 was greater than the cutoff. There was no correlation of any individual factors studied in these cases, including urinary tract infection and urinary BLCA-4. CONCLUSIONS: Elevated urinary BLCA-4 levels may accurately identify bladder cancer and distinguish these patients from normal individuals. There is no correlation of urinary BLCA-4 with a history of urinary tract infection, smoking, catheterization or cystitis considered independently. Urinary BLCA-4 determination appears to have high potential as a test for screening and monitoring bladder cancer in the general population and in groups at high risk for the disease, such as those with spinal cord injury.

Adult↗
PubMed2006

Nur77 forms novel nuclear structures upon DNA damage that cause transcriptional arrest.

The orphan nuclear receptor Nur77 has been implicated in both growth and apoptosis, and its function and activity can be modulated by cellular redistribution. Green fluorescent protein-tagged Nur77 was used to evaluate the role of Nur77 intracellular redistribution in response to genotoxic stress. Selected DNA damaging agents and transcription inhibition lead to rapid redistribution of Nur77 into nuclear structures distinct from conventional nuclear bodies. These nuclear bodies formed transiently were tightly bound to the nuclear matrix and conditions that lead to their appearance were associated with Nur77 transcriptional inhibition. The formation of Nur77 nuclear bodies might be involved in programmed cell death modulation upon exposure to DNA damaging agents that inhibit transcription by sequestrating this proapoptotic factor in dense nuclear structures.

Apoptosis↗
PubMed1999

Three-dimensional visualization of transcription sites and their association with splicing factor-rich nuclear speckles.

Transcription sites are detected by labeling nascent transcripts with BrUTP in permeabilized 3T3 mouse fibroblasts followed by laser scanning confocal microscopy. Inhibition and enzyme digestion studies confirm that the labeled sites are from RNA transcripts and that RNA polymerase I (RP I) and II (RP II) are responsible for nucleolar and extranucleolar transcription, respectively. An average of 2,000 sites are detected per nucleus with over 90% in the extranucleolar compartment where they are arranged in clusters and three-dimensional networklike arrays. The number of transcription sites, their three-dimensional organization and arrangement into functional zones (Wei et al. 1998) is strikingly maintained after extraction for nuclear matrix. Significant levels of total RP II mediated transcription sites (45%) were associated with splicing factor-rich nuclear speckles even though the speckles occupied <10% of the total extranucleolar space. Moreover, the vast majority of nuclear speckles (>90%) had moderate to high levels of associated transcription activity. Transcription sites were found along the periphery as well as inside the speckles themselves. These spatial relations were confirmed in optical sections through individual speckles and after in vivo labeling of nascent transcripts. Our results demonstrate that nuclear speckles and their surrounding regions are major sites of RP II-mediated transcription in the cell nucleus, and support the view that both speckle- and nonspeckle-associated regions of the nucleus contain sites for the coordination of transcription and splicing processes.

3T3 Cells↗