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H3 Acetylation (h3 + acetylation)

Distribution by Scientific Domains
Medical Sciences50%
Life Sciences50%

Kinds of H3 Acetylation

  • histone h3 acetylation
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    Selected Abstracts

    Chronic administration of valproic acid inhibits PC3 cell growth by suppressing tumor angiogenesis in vivo

    INTERNATIONAL JOURNAL OF UROLOGY, Issue 9 2007
    Dexuan Gao
    Aim: Chromatin remodeling agents such as histone deacetylase inhibitors have been shown to modulate gene expression in tumor cells and inhibit tumor growth and angiogenesis. We investigated the mechanisms of chronic valproic acid (VPA) inhibiting PC3 cell growth in the study. Methods: We established tumor xenografts of the PC3 cell line and investigated the effect of VPA chronic administration on tumor growth. Apoptosis in tumor tissue was measured using the TUNEL Detection Kit. We detected the effect of VPA chronic administration on histone acetylation; p21CIP1/WAF1 gene expression; vascular endothelial growth factor (VEGF) expression by reverse-transcription Polymerase Chain Reaction (PCR) analysis; immunohistochemistry; and Western Blotting. Result: In mouse models with established subcutaneous prostate (PC3), VPA treatment induced 70% inhibition of tumor growth without overt toxicity. Our result showed that chronic administration of VPA has an effect on tumor growth arrest and the effect was associated with increased histone acetylation, p21CIP1/WAF1 up-regulation, and VEGF down-regulation. Conclusion: We conclude that chronic VPA results in profound decreases in the proliferation of PC3 cells, not only by increasing histone H3 acetylation and up-regulating p21CIP1/WAF1 expression, but also by down-regulating VEGF. [source]

    Epigenetic modifications of SOX2 enhancers, SRR1 and SRR2, correlate with in vitro neural differentiation,

    JOURNAL OF NEUROSCIENCE RESEARCH, Issue 8 2008
    Marianna Sikorska
    Abstract SOX2 is a key neurodevelopmental gene involved in maintaining the pluripotency of stem cells and proliferation of neural progenitors and astroglia. Two evolutionally conserved enhancers, SRR1 and SRR2, are involved in controlling SOX2 expression during neurodevelopment; however, the molecular mechanisms regulating their activity are not known. We have examined DNA methylation and histone H3 acetylation at both enhancers in NT2-D1 progenitors, neurons and astrocytes, to establish the role of epigenetic mechanisms in cell-type-specific SOX2 expression. This study showed that 1) unmethylated DNA and acetylated histones at both enhancers correlated with a high level of SOX2 expression in proliferating neural progenitors and 2) reversible modifications of the SRR1 element were observed during gene reexpression in astrocytes, whereas permanent epigenetic marks on the SRR2 enhancer were seen in neurons where the gene was silenced. Taken together, these results are clear illustrations of cell-type-specific epigenomes and suggest mechanisms by which they may be created and maintained. © 2008 Wiley-Liss, Inc. [source]

    Differential Changes in MAP Kinases, Histone Modifications, and Liver Injury in Rats Acutely Treated With Ethanol

    ALCOHOLISM, Issue 9 2010
    Annayya R. Aroor
    Background:, Acute ethanol is known to affect cells and organs but the underlying molecular mechanisms are poorly explored. Recent developments highlight the potential importance of mitogen-activated protein kinases, MAPKs (i.e., ERK1/2, p38, and JNK1/2) signaling, and histone modifications (i.e., acetylation, methylation, and phosphorylation) in the actions of ethanol in hepatocytes. We have therefore investigated significance of these molecular steps in vivo using a model in which rats were acutely administered ethanol intraperitoneally (IP). Methods:, Ethanol was administered IP (3.5 gm/kg body weight) to 12-week-old male Sprague,Dawley rats. Liver was subsequently removed at 1 and 4 hours. Serum was used for alcohol and ALT assays. At the time of the removal of liver, small portions of each liver were formalin-fixed and stained with hematoxylin and eosin (H&E) and used for light microscopy. Western blot analysis was carried out with specific primary antibodies for various parameters. Results:, There were clear differences at 1 and 4 hours in blood ethanol, ALT, steatosis, and cleaved caspase 3. Apoptosis at 1 hour was followed by necrosis at 4 hours. Acute alcohol elicited a marked increase in the phosphorylation of ERK1/2 and moderate increases in the phosphorylation of p38 MAPK and JNK. Temporally different phosphorylation of histone H3 at ser-10 and ser-28 occurred and acetylation of histone H3 at lys 9 increased progressively. Conclusions:, There were distinct differences in the behavior of the activation of the 3 MAP kinases and histone modifications after acute short exposure of liver to ethanol in vivo. Although all 3 MAPKs were rapidly activated at 1 hour, the necrosis, occurring at 4 hours, correlated to sustained activation of ERK1/2. Transient activation of p38 is associated with rapid phosphorylation of histone H3, whereas prolonged activation of ERK1/2 is correlated to persistent histone H3 acetylation. [source]

    H4 acetylation does not replace H3 acetylation in chromatin remodelling and transcription activation of Adr1-dependent genes

    MOLECULAR MICROBIOLOGY, Issue 5 2006
    Eleonora Agricola
    Summary Histone acetylation regulates gene expression. Whether this is caused by a general increase in nucleosome fluidity due to charge neutralization or by a more specific code is still matter of debate. By using a set of glucose-repressed Adr1-dependent genes of Saccharomyces cerevisiae, whose transcription was previously shown to require both Gcn5 and Esa1, we asked how changes of histone acetylation patterns at the promoter nucleosomes regulate chromatin remodelling and activation. When the signal of glucose reduction reaches the cells, H4 acetylation is kept constant while an increase of H3 acetylation occurs, in an Adr1- and Gcn5-dependent manner. In cells lacking Gcn5 activity, the H3 acetylation increase does not occur and an unexpected increase of histone H4 acetylation is observed. Nevertheless, chromatin remodelling and transcription activation are impaired, suggesting that acetylation of H3 and H4 histones plays different roles. [source]

    The role of DNA methylation, nucleosome occupancy and histone modifications in paramutation

    THE PLANT JOURNAL, Issue 3 2010
    Max Haring
    Summary Paramutation is the transfer of epigenetic information between alleles that leads to a heritable change in expression of one of these alleles. Paramutation at the tissue-specifically expressed maize (Zea mays) b1 locus involves the low-expressing B, and high-expressing B-I allele. Combined in the same nucleus, B, heritably changes B-I into B,. A hepta-repeat located 100-kb upstream of the b1 coding region is required for paramutation and for high b1 expression. The role of epigenetic modifications in paramutation is currently not well understood. In this study, we show that the B, hepta-repeat is DNA-hypermethylated in all tissues analyzed. Importantly, combining B, and B-I in one nucleus results in de novo methylation of the B-I repeats early in plant development. These findings indicate a role for hepta-repeat DNA methylation in the establishment and maintenance of the silenced B, state. In contrast, nucleosome occupancy, H3 acetylation, and H3K9 and H3K27 methylation are mainly involved in tissue-specific regulation of the hepta-repeat. Nucleosome depletion and H3 acetylation are tissue-specifically regulated at the B-I hepta-repeat and associated with enhancement of b1 expression. H3K9 and H3K27 methylation are tissue-specifically localized at the B, hepta-repeat and reinforce the silenced B, chromatin state. The B, coding region is H3K27 dimethylated in all tissues analyzed, indicating a role in the maintenance of the silenced B, state. Taken together, these findings provide insight into the mechanisms underlying paramutation and tissue-specific regulation of b1 at the level of chromatin structure. [source]

    Role of osteopontin in synovial Th17 differentiation in rheumatoid arthritis

    ARTHRITIS & RHEUMATISM, Issue 10 2010
    Guangjie Chen
    Objective Osteopontin (OPN) that is aberrantly produced in rheumatoid synovium is thought to play an important role in rheumatoid arthritis (RA). This study was undertaken to investigate the role of OPN in the differentiation and accumulation of Th17 cells in rheumatoid synovium. Methods Peripheral blood mononuclear cells and purified CD4+ T cells derived from patients with RA or healthy controls were used to test the effect of OPN in vitro. Cytokine expression was determined by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. Intracellular staining and flow cytometry were used to detect the percentages of Th17 cells and OPN receptors. Signaling and molecular events were analyzed by immunoblotting and chromatin immunoprecipitation. Results The levels of OPN correlated significantly with interleukin-17 (IL-17) production and the frequency of Th17 cells in the synovial fluid (SF) of RA patients. Endogenous OPN produced in RA SF was responsible for markedly increased production of IL-17 in T cells, which was blocked by OPN antibody. The effect of OPN in Th17 differentiation was mediated through a mechanism independent of the IL-6/STAT-3 pathway or other cytokines and specifically involved the OPN receptors CD44 and CD29 and the transcription factor retinoic acid,related orphan receptor (ROR). Furthermore, OPN was found to induce H3 acetylation of the IL17A gene promoter, mainly through the CD44 binding domain in CD4+ T cells, allowing the interaction of the IL17A gene locus with ROR. Conclusion This study reveals new evidence of the critical role of OPN in Th17 differentiation in rheumatoid synovitis. [source]

    Laboratory correlates for a phase II trial of romidepsin in cutaneous and peripheral T-cell lymphoma

    BRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2010
    Susan E. Bates
    Summary Romidepsin has shown promise in the treatment of T-cell lymphomas, and so we evaluated molecular endpoints gathered from 61 patients enrolled on a phase II trial of romidepsin in cutaneous and peripheral T-cell lymphoma at the National Institutes of Health. The endpoints included histone H3 acetylation and ABCB1 gene expression in peripheral blood mononuclear cells (PBMCs); ABCB1 gene expression in tumour biopsy samples; and blood fetal haemoglobin levels (HbF), all of which were increased following romidepsin treatment. The fold increase in histone acetylation in PBMCs at 24 h was weakly to moderately well correlated with the pharmacokinetic parameters Cmax and area under the curve (AUC)last (, = 0·37, P = 0·03 and , = 0·36, P = 0·03 respectively) and inversely associated with clearance (, = ,0·44; P = 0·03). Histone acetylation in PBMCs at 24 h was associated with response (P = 0·026) as was the increase in fetal haemoglobin (P = 0·014); this latter association may be due to the longer on-study duration for patients with disease response. Together, these results suggest that pharmacokinetics may be an important determinant of response to histone deacetylase inhibitors (HDIs) , the association with histone acetylation in PBMCs at 24 h is consistent with a hypothesis that potent HDIs are needed for a critical threshold of drug exposure and durable activity. [source]