The nucleus of the eukaryotic cell must carry out many functions simultaneously. These tasks include ensuring that the cell is continuously supplied with an appropriate, changing set of proteins on its way through cell divisions and differentiation. During these processes, the integrity of the genetic material must be maintained against ...

A series of sulfonamide hydroxamic acids and anilides have been synthesized and studied as histone deacetylase (HDAC) inhibitors that can induce hyperacetylation of histones in human cancer cells. The inhibition of HDAC activity represents a novel approach for intervening in cell cycle regulation. The lead candidates were screened in a ...

Remodeling of the chromatin template by inhibition of HDAC activities represents a potential transcriptional therapy for neoplastic disease. A number of HDAC inhibitors that modulate in vitro cell growth and differentiation have been developed. We analyzed the effects of TSA, a specific and potent HDAC inhibitor, on the human hepatoma ...

Acetylation of histone residues regulates the expression of inflammatory genes and is controlled by the activities of histone acetyltransferases (HAT) and histone deacetylases (HDAC). Analysis of histone acetylation in human cells is limited by the large numbers needed to perform activity assays or Western blotting. We have used flow cytometry ...

Increasing cellular G-actin, using latrunculin B, in either intact or permeabilized rat peritoneal mast cells, caused translocation of both actin and an actin regulatory protein, cofilin, into the nuclei. The effect was not associated with an increase in the proportion of apoptotic cells. The major part of the nuclear actin ...

We have recently gained new insight into the mechanisms involved in nuclear envelope breakdown, the irreversible step that commits a cell to the M phase. Results from mammalian cell and starfish oocyte studies suggest that mechanical forces of the cytoskeleton, as well as biochemical disassembly of nuclear envelope protein complexes, ...

The fungal metabolite apicidin (cyclo(N-O-methyl-L-tryptophanyl-L-isoleucinyl-D-pipecolinyl-L-2-amino-8-oxodecanoyl)) inhibited the growth of HL-60 cells in a concentration-dependent manner (100-1000 nM). At higher concentrations (>300 nM), cell death was induced. At 100 nM, it induced hyperacetylation of histone H4 time-dependently, while trichostatin A induced transient hyperacetylation. Apicidin (10-100 nM) increased the cells having nitroblue ...

Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a tumor suppressor that causes cell cycle arrest. Lack of a nuclear locator sequence and a function in the cytosolic phosphatidylinositol 3'-kinase/Akt pathway diverted its study from the nucleus. However, immunohistochemistry revealed PTEN in the nucleus of normal cells and ...

Micronucleus formation in fish erythrocytes, as an indicator of chromosomal damage, has been increasingly used to detect the genotoxic potential of environmental contaminants. Nucleolar organizer regions (NORs) stained with colloidal silver techniques indicate sites of active RNA transcription. The number and size of NORs in interphase nuclei reflect cellular activities ...

I argue that carcinogenic insults injure many cells rather than mutate a few. This results from evidence that such insults convert too many cells to a precancerous state and that too many of the converted cells then revert to plausibly involve mutation and its repair; from evidence that the delays ...

Histone deacetylase inhibitors (HDAC inhibitors) represent a novel class of antineoplastic agents that act by promoting acetylation of histones, leading in turn to uncoiling of chromatin and activation of a variety of genes implicated in the regulation of cell surivival, proliferation, differentiation, and apoptosis. The major classes of HDIs include ...

A confocal Raman microscope is used to study the protein distribution inside biological cells. It is shown that high quality Raman imaging of the protein distribution can be obtained using confocal nonresonant Raman imaging (lambda(exc) = 647.1 nm). The results are shown for two different human cell types. Perpheral blood ...

We investigated a set of cell lines as to their sensitivity to proliferation inhibition, on the one side, and apoptosis induction, on the other, by the core histone deacetylase inhibitors butyrate and trichostatin A (TSA), respectively. The results can be summarized as follows: (i) the investigated cell lines can be ...

Oocytes and embryos of many species, including mammals, contain a unique linker (H1) histone, termed H1oo in mammals. It is uncertain, however, whether other H1 histones also contribute to the linker histone complement of these cells. Using immunofluorescence and radiolabeling, we have examined whether histone H10, which frequently accumulates in ...

The stem-loop binding protein (SLBP) binds to the 3' end of histone mRNA and participates in 3'-processing of the newly synthesized transcripts, which protects them from degradation, and probably also promotes their translation. In proliferating cells, translation of SLBP mRNA begins at G1/S and the protein is degraded following DNA ...

An immunohistochemical technique has been used to localise nuclear oncoproteins in the groove of Ranvier. The densely packed cells deep in the groove were immunoreactive positive for the myc protein. Cells and matrix in the same location were immunoreactive positive for the jun protein. These findings confirm the presence of ...

We have found that cells derived from heterokaryons (HK) showing phenotypical traits, coded by the nucleus of one parental strain and by the cytoplasm of the other, may produce mitotic progeny in which the second nucleus is apparently present but not expressed. This 'concealed' nucleus can be forced to expression ...

Inhibitors of histone deacetylase activity are emerging as a potentially important new class of anticancer agents. In the current studies, exposing A2780 ovarian cancer cells to the histone deacetylase inhibitor trichostatin A (TSA) produced a marked change in cellular morphology, proliferation, and differentiation. Within 24 h of TSA treatment, there ...

We are investigating the mechanism responsible for the overexpression of the keratin 18 (K18) gene in tumorigenic clones from the SW613-S human colon carcinoma cell line, as compared with non-tumorigenic clones. We have previously shown that this mechanism affects the minimal K18 promoter (TATA box and initiation site). We report ...

High mobility group 1 (HMGB1) protein is both a nuclear factor and a secreted protein. In the cell nucleus it acts as an architectural chromatin-binding factor that bends DNA and promotes protein assembly on specific DNA targets. Outside the cell, it binds with high affinity to RAGE (the receptor for ...

Reversible protein acetylation is established as a modification of major regulatory significance. In particular, histone acetylation regulates access to genetic information in eukaryotes. For example, class I and class II histone deacetylases are regulatory components of corepressor complexes involved in cell cycle progression and differentiation. Here, we have investigated the ...

E2F-6 contributes to gene silencing in a manner independent of retinoblastoma protein family members. To better elucidate the molecular mechanism of repression by E2F-6, we have purified the factor from cultured cells. E2F-6 is found in a multimeric protein complex that contains Mga and Max, and thus the complex can ...

The short-chain fatty acid (SCFA) butyrate is produced via anaerobic bacterial fermentation within the colon and is thought to be protective in regard to colon carcinogenesis. Although butyrate (C4) is considered the most potent of the SCFA, a variety of other SCFA also exist in the colonic lumen. Butyrate is ...

Faithful inheritance of the chromatin structure is essential for maintaining the gene expression integrity of a cell. Histone modification by acetylation and deacetylation is a critical control of chromatin structure. In this study, we test the hypothesis that histone deacetylase 1 (HDAC1) is physically associated with a basic component of ...

Histone deacetylase inhibitors that increase histone acetylation on transformed cells are being investigated as unique anticancer drugs. The aim of this investigation was to evaluate an antiproliferative activity of the histone deacetylase inhibitors sodium butyrate (NaBT) and trichostatin A on 5 glioma cell lines, T98G, A172, U-87 MG, U-118 MG, ...

Nuclear envelope-limited chromatin sheets (ELCS) are enigmatic membranous structures of uncertain function. This study describes the induction of ELCS in p53 mutated Burkitt's lymphoma cell lines after treatment with irradiation or the microtubule inhibitor, SK&F 96365. Both treatments evoked similar mitotic death, involving metaphase arrest followed by extensive endopolyploidisation and ...

The human replication protein Cdc6p is translocated from its chromatin sites to the cytoplasm during the replication phase (S phase) of the cell cycle. However, the amounts of Cdc6p on chromatin remain high during S phase implying either that displaced Cdc6p can rebind to chromatin, or that Cdc6p is synthesized ...

A project designed to identify genes involved in the control of cell proliferation and apoptosis in acute myeloid leukemia (AML) led to the cloning of a novel member of the SNF2 (sucrose non-fermenter) family, a group of proteins that remodels chromatin and functions in transcription, repair, recombination, and methylation. This ...

In mammalian somatic cells, the X chromosome is active in XY males, whereas one X chromosome is inactivated in XX females. On the active male X chromosome, the XIST and TSIX genes are transcribed in undifferentiated cells of pre-implantation embryos (undifferentiated state) and then down-regulated upon cell differentiation (differentiated state). ...

Growth-inhibitory effects on DS19 mouse erythroleukemia cells were seen in the micromolar concentration range with allicin and S-allylmercaptocysteine and in the millimolar range with allyl butyrate, allyl phenyl sulfone, and S-allyl cysteine. Increased acetylation of histones was induced by incubation of cells with the allyl compounds at concentrations similar to ...

The dynamic state of post-translational acetylation of eukaryotic histones is maintained by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HATs and HDACs have been shown to be components of various regulatory protein complexes in the cell. Their enzymatic activities, intracellular localization and substrate specificities are regulated in a complex, cell ...

The cell nucleus is separated from the rest of the cell by the nuclear envelope. The nuclear envelope, nuclear envelope proteins and nuclear lamina organise the structure of the entire nucleus and the chromatin via a myriad of interactions. These interactions are dynamic, change with the change (progress) of the ...

It is remarkable that mammalian somatic cell nuclei can form whole individuals if they are transferred to enucleated oocytes. Advancements in nuclear transfer technology can now be applied for genetic improvement and increase of farm animals, rescue of endangered species, and assisted reproduction and tissue engineering in humans. Since July ...

Previous studies have shown that changes in the affinity of the hamster Orc1 protein for chromatin during the M-to-G(1) transition correlate with the activity of hamster origin recognition complexes (ORCs) and the appearance of prereplication complexes at specific sites. Here we show that Orc1 is selectively released from chromatin as ...

Chromatin of Trypanosoma cruzi is known to be organized in classical nucleosomal filaments, but surprisingly, these filaments do not fold in visible chromosomes and the nuclear envelope is preserved during cell division. Our hypothesis about the role of chromatin structure in regulating gene expression and, more generally, cell functioning, pressed ...

The few viable clones obtained at the end of a typical cloning experiment are genetic copies of the donor cell genome of a non-reproductive (somatic) or embryonic cell used for nuclear transfer. Nuclear totipotency has to be reestablished by erasing epigenetic constraints imposed on the donor genome during differentiation in ...

Polyglutamine diseases include at least nine neurodegenerative disorders, each caused by a CAG repeat expansion in a different gene. Accumulation of mutant polyglutamine-containing proteins occurs in patients, and evidence from cell culture and animal experiments suggests the nucleus as a site of pathogenesis. To understand the consequences of nuclear accumulation, ...

Cell differentiation may depend in part upon a type of unbalanced growth in which several cell cycles occur with a reduced level of total protein synthesis. During this period the synthesis of the chromatin protein HMG-I/Y is reduced since its synthesis is correlated with that of total protein. The synthesis ...

Splicing snRNPs (small nuclear ribonucleoproteins) are essential sub-units of the spliceosome. Here we report the establishment of stable cell lines expressing fluorescently tagged SmB, a core snRNP protein. Analysis of these stable cell lines has allowed us to characterize the nuclear pathway that leads to snRNP accumulation in nuclear speckles ...

The chromosomes of eukaryotic cells are separated from the cytoplasm by the nuclear envelope. The nuclear envelope includes two riveted membranes, plus embedded pore complexes that mediate nuclear import and export. In this sense, the nuclear envelope is truly a border zone. However, the envelope also links directly to chromosomes, ...

Intranuclear lamin foci or speckles have been observed in various cell types. In order to explore the possibility of changes in internal lamin organization during muscle differentiation, we have examined the appearance of A-type lamin speckles that associate with RNA splicing factor speckles in C2C12 myoblasts and myotubes. Lamin speckles ...

Characteristics of spermatogonia were determined in the C57BL/6J strain mouse using high-resolution light microscopy of plastic-embedded tissues and identifying cells during stages of the spermatogenic cycle. The frequency of expecting each spermatogonial cell type was a major factor in identifying and categorizing various cell types. Although numerous characteristics were described, ...

PURPOSE: Previous studies indicated that cells whose chromatin is naturally compacted at the time of radiation are hypersensitive to radiation-induced killing, primarily by single-hit inactivation. Some chemicals that are known to promote chromatin compaction in interphase cells are here investigated for their radiosensitizing potential. MATERIALS AND METHODS: Okadaic acid (OA), ...

An enzymatic mechanism has been proposed by which biotinidase may catalyze biotinylation of histones. Here, human cells were found to covalently bind biotin to histones H1, H2A, H2B, H3, and H4. Cells respond to proliferation with increased biotinylation of histones; biotinylation increases early in the cell cycle and remains increased ...

Enzymes which affect histone acetylation status have been shown to play an important role in determining transcriptional activity in chromatin through conformational modification of its structure. Since the timely presence of such enzymes may be of critical importance, our experiments were designed to determine whether the level of expression of ...

In all eukaryotes, multisubunit histone acetyltransferase (HAT) complexes acetylate the highly conserved lysine residues in the amino-terminal tails of core histones to regulate chromatin structure and gene expression. One such complex in yeast, NuA4, specifically acetylates nucleosome-associated histone H4. Recent studies have revealed that NuA4 comprises at least 11 subunits, ...

The HIRA gene encodes a nuclear protein with histone-binding properties that have been conserved from yeast to humans. Hir1p and Hir2p, the two HIRA homologues in Saccharomyces cerevisiae, are transcriptional co-repressors whose action resides at the chromatin level and occurs in a cell-cycle-regulated fashion. In mammals, HIRA is an essential ...

CENP-H has recently been discovered as a constitutive component of the centromere that co-localizes with CENP-A and CENP-C throughout the cell cycle. The precise function, however, remains poorly understood. We examined the role of CENP-H in centromere function and assembly by generating a conditional loss-of-function mutant in the chicken DT40 ...

Mutation of the Adenomatous Polyposis Coli (APC) gene is an early step in the development of colorectal carcinomas. To provide clues for APC's role in tumor suppression, the subcellular distribution of APC was studied, and APC was found to localize to both the cytoplasm and the nucleus of normal human ...

Spermatogenesis is a complex differentiation process which is characterised, among other features, by conspicuous stage-specific nuclear events such as the pairing of homologous chromosomes coupled with the formation of synaptonemal complexes, the replacement of histones with sperm-specific proteins during spermiogenesis and, as a result, chromatin condensation and its inactivation in ...