Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: HUMANGGP:040116 (histone)
 44,835 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of several dehydration treatments on the synaptonemal complex (SC), histone solubility in 2.0 M NaCl, and histone-DNA interaction in unfixed rat spermatocytes were evaluated. Freeze substitution with ethanol or dehydration with polyethylene glygol resulted in loss of the SC, preservation of histone solubility and DNA-histone salt linkages. Dehydration with ethylene gylcol or hexylene glycol resulted in preservation of SC with a clear delineation of attachment of the chromatin fibrils to the lateral elements, but a loss of histone solubility and histone-DNA linkages. Dehydration to a fifty percent concentration with glycerol with completion of dehydration with ethylene glycol had the same effect but also resulted in an even distribution of chromatin fibrils. Dehydration with glycerol alone resulted in clumping of chromatin and loss of SC structure, histone solubility and histone-DNA linkages. Partial dehydration to a fifty percent concentration with these three solvents followed by freeze substitution with ethanol resulted in the loss of SC structure and histone solubility but the preservation of histone-DNA linkages. It is likely that these nonaqueous solvents affected the histone hydrophobic groups and thereby altered histone conformation and interactions. These alterations, depending on the treatment used, resulted in the loss or preservation of SC, histone solubility and histone-DNA interactions thereby indicating that the hydrophobic interactions of the histones are crucial for the preservation of these feature of meiotic chromosomes. These results also demonstrate that neither does the preservation of the histone-DNA salt linkages suffice for the preservation of the SC nor does their disruption necessarily result in its loss. The lysine-rich histones, particularly that one unique to meiotic cells, may through their interactions play a crucial role in SC structure.
 ...
PMID:Cytochemical and ultrastructural studies on the synaptonemal complex of rat spermatocytes. 32 69

Members of the Mad family of bHLH-Zip proteins heterodimerize with Max to repress transcription in a sequence-specific manner. Transcriptional repression by Mad:Max heterodimers is mediated by ternary complex formation with either of the corepressors mSin3A or mSin3B. We report here that mSin3A is an in vivo component of large, heterogeneous multiprotein complexes and is tightly and specifically associated with at least seven polypeptides. Two of the mSin3A-associated proteins, p50 and p55, are highly related to the histone deacetylase HDAC1. The mSin3A immunocomplexes possess histone deacetylase activity that is sensitive to the specific deacetylase inhibitor trapoxin. mSin3A-targeted repression of a reporter gene is reduced by trapoxin treatment, suggesting that histone deacetylation mediates transcriptional repression through Mad-Max-mSin3A multimeric complexes.
 ...
PMID:Histone deacetylase activity is required for full transcriptional repression by mSin3A. 915 Jan 33

Recent works demonstrated that some transcriptional repressors recruit histone deacetylases (HDACs) either through direct interaction, or as a member of a multisubunit repressing complex containing other components referred to as corepressors. For instance, the bHLH-Zip transcriptional repressors MAD/MXI recruit HDACs together with the mSIN3 corepressors, whereas unliganded nuclear receptors contact another corepressor, SMRT (or its relative N-CoR), which, in turn, associates with both mSIN3 and HDACs to form the repressor complex. Recently, we reported that SMRT also directly associates with LAZ3(BCL-6), a POZ/Zn finger transcriptional repressor involvedin the pathogenesis of non-Hodgkin lymphomas. However, whether LAZ3 recruits the HDACs-containing repression complex is currently unknown. We report here that LAZ3 associates with corepressor mSIN3A both in vivo and in vitro , and found that a central region, which harbours autonomous repression activity, is mainly responsible for this interaction. Conversely, the N-terminal half of mSIN3A is both necessary and sufficient to bind LAZ3. Moreover, we show that LAZ3 also interacts with an HDAC (HDAC-1) through its POZ domain in vitro while the immunoprecipitation of LAZ3 results in the coretention of an endogenous HDAC activity in vivo . Finally, inhibitors of HDACs significantly reduce the LAZ3-mediated repression. Taken together, we conclude that LAZ3 recruits a repressing complex containing SMRT, mSIN3A and a HDAC, and that its full repressing potential on transcription requires HDACs activity. Our results identify HDACs as molecular targets of LAZ3 oncogene and further strengthen the connection between aberrant chromatin acetylation and human cancers.
 ...
PMID:The LAZ3(BCL-6) oncoprotein recruits a SMRT/mSIN3A/histone deacetylase containing complex to mediate transcriptional repression. 975 32

Histone deacetylase inhibitors are emerging therapeutic agents for cancer. In addition to effecting hyperacetylation of core histones, they have been shown to induce biologic effects such as cell cycle redistribution, cytostasis and in certain cases apoptosis in a variety of cell lines. In this study, the purpose was to investigate the effects of Trichostatin A (TSA) - the most potent histone deacetylase inhibitor identified to date - in human erythroleukemic K562 cells. Further aims were to examine the effect of TSA pre-treatment on the chemosensitivity of the cells to the anthracycline, doxorubicin, and on radiosensitivity. In all experiments the cells were treated with 0.2, 0.5 and 2 mM TSA for 24 h prior to analysis for histone acetylation status, cell growth and survival. In parallel assays, TSA treated cells were exposed to doxorubicin or g-radiation and subsequently analyzed for clonogenic survival. The findings indicated that TSA exhibits potent histone deacetylase inhibitor activity in K562 cells, resulting in hyperacetylation of histones 3 and 4 at the concentrations tested. Furthermore, treatment of cells with TSA resulted in dose-dependent inhibition of proliferation, reduction in clonogenic survival and induction of apoptosis. Moreover, the findings of clonogenic survival assays indicated that pre-treatment of K562 cells with TSA augmented the cytotoxic potency of doxorubicin. The magnitude of sensitization to 10 mM doxorubicin-mediated cell death was approximately 2-fold in cells that were treated with 0.2 mM TSA and 5-fold in cells exposed to 0.5 and 2 mM TSA, compared to cells that had not been pre-treated with the histone deacetylase inhibitor. Similarly, exposure of K562 cells to TSA prior to irradiation resulted in dose-dependent radiosensitization. The dose modification factors at D(37) were calculated to be 1.3, 1.6 and 2.5 for cells treated with 0.2, 0.5 and 2 mM TSA, respectively. These findings provide additional evidence that histone deacetylase inhibitors can increase the cytotoxic efficiency of chemotherapeutic drugs, particularly those which target DNA, and can enhance the sensitivity of cells to g-radiation. More generally, the results support the development of histone deacetylase inhibitors as potential clinical chemo- and radio-sensitizers.
Hell J Nucl Med
PMID:Radio- and chemo-sensitization of human erythroleukemic K562 cells by the histone deacetylase inhibitor Trichostatin A. 1584 Dec 97

Leaf senescence is the final stage of leaf development and is finely regulated via a complex genetic regulatory network incorporating both developmental and environmental factors. In an effort to identify negative regulators of leaf senescence, we screened activation-tagged Arabidopsis lines for mutants that exhibit a delayed leaf senescence phenotype. One of the mutants (ore7-1D) showed a highly significant delay of leaf senescence in the heterozygous state, leading to at least a twofold increase in leaf longevity. The activated gene (ORE7/ESC) encoded a protein with an AT-hook DNA-binding motif; such proteins are known to co-regulate transcription of genes through modification of chromatin architecture. We showed that ORE7/ESC, in addition to binding to a plant AT-rich DNA fragment, could also modify the chromatin architecture, as illustrated by an altered distribution of a histone-GFP fusion protein in the nucleus of the mutant. Globally altered gene expression, shown by microarray analysis, also indicated that activation of ORE7/ESC results in a younger condition in the mutant leaves. We propose that ectopically expressed ORE7/ESC is negatively regulating leaf senescence and suggest that the resulting chromatin alteration may have a role in controlling leaf longevity. Interestingly, activation of ORE7/ESC also led to a highly extended post-harvest storage life.
 ...
PMID:Overexpression of a chromatin architecture-controlling AT-hook protein extends leaf longevity and increases the post-harvest storage life of plants. 1797 Oct 39

Leaf senescence, the final step of leaf development, involves extensive reprogramming of gene expression. Here, we show that these processes include discrete changes of epigenetic indexing, as well as global alterations in chromatin organization. During leaf senescence, the interphase nuclei show a decondensation of chromocenter heterochromatin, and changes in the nuclear distribution of the H3K4me2, H3K4me3, and the H3K27me2 and H3K27me3 histone modification marks that index active and inactive chromatin, respectively. Locus-specific epigenetic indexing was studied at the WRKY53 key regulator of leaf senescence. During senescence, when the locus becomes activated, H3K4me2 and H3K4me3 are significantly increased at the 5' end and at coding regions. Impairment of these processes is observed in plants overexpressing the SUVH2 histone methyltransferase, which causes ectopic heterochromatization. In these plants the transcriptional initiation of WRKY53 and of the senescence-associated genes SIRK, SAG101, ANAC083, SAG12 and SAG24 is inhibited, resulting in a delay of leaf senescence. In SUVH2 overexpression plants, significant levels of H3K27me2 and H3K27me3 are detected at the 5'-end region of WRKY53, resulting in its transcriptional repression. Furthermore, SUVH2 overexpression inhibits senescence-associated global changes in chromatin organization. Our data suggest that complex epigenetic processes control the senescence-specific gene expression pattern.
 ...
PMID:Epigenetic programming via histone methylation at WRKY53 controls leaf senescence in Arabidopsis thaliana. 1914 96

Very little is known about the molecular origin of the large phenotypic differentiation between genotypes arising from somatic chromosome set doubling and their diploid parents. In this study, the anatomy and physiology of diploid (2x) and autotetraploid (4x) Rangpur lime (Citrus limonia Osbeck) seedlings has been characterized. Growth of 2x was more vigorous than 4x although leaves, stems, and roots of 4x plants were thicker and contained larger cells than 2x that may have a large impact on cell-to-cell water exchanges. Leaf water content was higher in 4x than in 2x. Leaf transcriptome expression using a citrus microarray containing 21 081 genes revealed that the number of genes differentially expressed in both genotypes was less than 1% and the maximum rate of gene expression change within a 2-fold range. Six up-regulated genes in 4x were targeted to validate microarray results by real-time reverse transcription-PCR. Five of these genes were apparently involved in the response to water deficit, suggesting that, in control conditions, the genome expression of citrus autotetraploids may act in a similar way to diploids under water-deficit stress condition. The sixth up-regulated gene which codes for a histone may also play an important role in regulating the transcription of growth processes. These results show that the large phenotypic differentiation in 4x Rangpur lime compared with 2x is not associated with large changes in genome expression. This suggests that, in 4x Rangpur lime, subtle changes in gene expression may be at the origin of the phenotypic differentiation of 4x citrus when compared with 2x.
 ...
PMID:Large changes in anatomy and physiology between diploid Rangpur lime (Citrus limonia) and its autotetraploid are not associated with large changes in leaf gene expression. 2127 38

Sugar beet (Beta vulgaris) chromosomes consist of large heterochromatic blocks in pericentromeric, centromeric, and intercalary regions comprised of two different highly abundant DNA satellite families. To investigate DNA methylation at single base resolution at heterochromatic regions, we applied a method for strand-specific bisulfite sequencing of more than 1,000 satellite monomers followed by statistical analyses. As a result, we uncovered diversity in the distribution of different methylation patterns in both satellite families. Heavily methylated CG and CHG (H=A, T, or C) sites occur more frequently in intercalary heterochromatin, while CHH sites, with the exception of CAA, are only sparsely methylated, in both intercalary and pericentromeric/centromeric heterochromatin. We show that the difference in DNA methylation intensity is correlated to unequal distribution of heterochromatic histone H3 methylation marks. While clusters of H3K9me2 were absent from pericentromeric heterochromatin and restricted only to intercalary heterochromatic regions, H3K9me1 and H3K27me1 were observed in all types of heterochromatin. By sequencing of a small RNA library consisting of 6.76 million small RNAs, we identified small interfering RNAs (siRNAs) of 24 nucleotides in size which originated from both strands of the satellite DNAs. We hypothesize an involvement of these siRNAs in the regulation of DNA and histone methylation for maintaining heterochromatin.
 ...
PMID:Epigenetic profiling of heterochromatic satellite DNA. 2159

Leaf primordia are generated around the shoot apical meristem. Mutation of the ASYMMETRIC LEAVES2 (AS2) gene of Arabidopsis thaliana results in defects in repression of the meristematic and indeterminate state, establishment of adaxial-abaxial polarity and left-right symmetry in leaves. AS2 represses transcription of meristem-specific class 1 KNOX homeobox genes and of the abaxial-determinant genes ETTIN/ARF3, KANADI2 and YABBY5. To clarify the role of AS2 in the establishment of leaf polarity, we isolated mutations that enhanced the polarity defects associated with as2. We describe here the enhancer-of-asymmetric-leaves-two1 (east1) mutation, which caused the formation of filamentous leaves with abaxialized epidermis on the as2-1 background. Levels of transcripts of class 1 KNOX and abaxial-determinant genes were markedly higher in as2-1 east1-1 mutant plants than in the wild-type and corresponding single-mutant plants. EAST1 encodes the histone acetyltransferase ELONGATA3 (ELO3), a component of the Elongator complex. Genetic analysis, using mutations in genes involved in the biogenesis of a trans-acting small interfering RNA (ta-siRNA), revealed that ELO3 mediated establishment of leaf polarity independently of AS2 and the ta-siRNA-related pathway. Treatment with an inhibitor of histone deacetylases (HDACs) caused additive polarity defects in as2-1 east1-1 mutant plants, suggesting the operation of an ELO3 pathway, independent of the HDAC pathway, in the determination of polarity. We propose that multiple pathways play important roles in repression of the expression of class 1 KNOX and abaxial-determinant genes in the development of the adaxial domain of leaves and, thus, in the establishment of leaf polarity.
 ...
PMID:Asymmetric leaves2 and Elongator, a histone acetyltransferase complex, mediate the establishment of polarity in leaves of Arabidopsis thaliana. 2170 Jul 21

Leaf senescence is the orderly dismantling of older tissue that allows recycling of nutrients to developing portions of the plant and is accompanied by major changes in gene expression. Histone modifications correlate to levels of gene expression, and this study utilizes ChIP-seq to classify activating H3K4me3 and silencing H3K27me3 marks on a genome-wide scale for soil-grown mature and naturally senescent Arabidopsis leaves. ChIPnorm was used to normalize data sets and identify genomic regions with significant differences in the two histone methylation patterns, and the differences were correlated to changes in gene expression. Genes that showed an increase in the H3K4me3 mark in older leaves were senescence up-regulated, while genes that showed a decrease in the H3K4me3 mark in the older leaves were senescence down-regulated. For the H3K27me3 modification, genes that lost the H3K27me3 mark in older tissue were senescence up-regulated. Only a small number of genes gained the H3K27me3 mark, and these were senescence down-regulated. Approximately 50% of senescence up-regulated genes lacked the H3K4me3 mark in both mature and senescent leaf tissue. Two of these genes, SAG12 and At1g73220, display strong senescence up-regulation without the activating H3K4me3 histone modification. This study provides an initial epigenetic framework for the developmental transition into senescence.
 ...
PMID:Genome-wide evaluation of histone methylation changes associated with leaf senescence in Arabidopsis. 2242 74


1 2 3 Next >>