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H3 Lysine (h3 + lysine)

Distribution by Scientific Domains
Life Sciences81%

Kinds of H3 Lysine

  • histone h3 lysine
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    Selected Abstracts

    Epigenetic control of translation regulation: Alterations in histone H3 lysine 9 post-translation modifications are correlated with the expression of the translation initiation factor 2B (Eif2b5) during thermal control establishment

    DEVELOPMENTAL NEUROBIOLOGY, Issue 2 2010
    Tatiana Kisliouk
    Abstract Thermal control set point is regulated by thermosensitive neurons of the preoptic anterior hypothalamus (PO/AH) and completes its development during postnatal critical sensory period. External stimuli, like increase in environmental temperature, influence the neuronal protein repertoire and, ultimately, cell properties via activation or silencing of gene transcription, both of which are regulated by the "histone code."" Here, we demonstrated an increase in global histone H3 lysine 9 (H3K9) acetylation as well as H3K9 dimethylation in chick PO/AH during heat conditioning at the critical period of sensory development. In contrast to the global profile of H3K9 modifications, acetylation and dimethylation patterns of H3K9 at the promoter of the catalytic subunit of eukaryotic translation initiation factor 2B (Eif2b5) were opposite to each other. During heat conditioning, there was an increase in H3K9 acetylation at the Eif2b5 promoter, simultaneously with decrease in H3K9 dimethylation. These alterations coincided with Eif2b5 mRNA induction. Moreover, exposure to excessive heat during the critical period resulted in long-term effect on both H3K9 tagging at the Eif2b5 promoter and Eif2b5 mRNA expression. These data suggest a role for dynamic H3K9 post-translational modifications in global translation regulation during the thermal control establishment. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2010 [source]

    PRECLINICAL STUDY: BRIEF REPORT: Epigenetic modulation at the CCR2 gene correlates with the maintenance of behavioral sensitization to methamphetamine

    ADDICTION BIOLOGY, Issue 3 2010
    Daigo Ikegami
    ABSTRACT The intermittent administration of methamphetamine produces behavioral sensitization to methamphetamine. In the limbic forebrain, mainly including the nucleus accumbens, of mice that had been intermittently treated with methamphetamine, we found a significant increase in mRNA of a chemokine, CCR2. This increase was accompanied by a significant increase in histone H3 lysine 4 (H3K4) trimethylation at its promoter. Interestingly, the maintenance of sensitization to methamphetamine-induced hyperlocomotion was significantly decreased in CCR2 knockout mice. These findings suggest that increased CCR2 associated with epigenetic modification after the intermittent administration of methamphetamine may be associated with the maintenance of sensitization to methamphetamine-induced hyperlocomotion. [source]

    Obesity and metabolic syndrome in histone demethylase JHDM2a-deficient mice

    GENES TO CELLS, Issue 8 2009
    Takeshi Inagaki
    Histone H3 lysine 9 (H3K9) methylation is a crucial epigenetic mark of heterochromatin formation and transcriptional silencing. Recent studies demonstrated that most covalent histone lysine modifications are reversible and the jumonji C (JmjC)-domain-containing proteins have been shown to possess such demethylase activities. However, there is little information available on the biological roles of histone lysine demethylation in intact animal model systems. JHDM2A (JmjC-domain-containing histone demethylase 2A, also known as JMJD1A) catalyses removal of H3K9 mono- and dimethylation through iron and ,-ketoglutarate dependent oxidative reactions. Here, we demonstrate that JHDM2a also regulates metabolic genes related to energy homeostasis including anti-adipogenesis, regulation of fat storage, glucose transport and type 2 diabetes. Mice deficient in JHDM2a (JHDM2a,/,) develop adult onset obesity, hypertriglyceridemia, hypercholesterolemia, hyperinsulinemia and hyperleptinemia, which are hallmarks of metabolic syndrome. JHDM2a,/, mice furthermore exhibit fasted induced hypothermia indicating reduced energy expenditure and also have a higher respiratory quotient indicating less fat utilization for energy production. These observations may explain the obesity phenotype in these mice. Thus, H3K9 demethylase JHDM2a is a crucial regulator of genes involved in energy expenditure and fat storage, which suggests it is a previously unrecognized key regulator of obesity and metabolic syndrome. [source]

    RBP2 is an MRG15 complex component and down-regulates intragenic histone H3 lysine 4 methylation

    GENES TO CELLS, Issue 6 2007
    Tomohiro Hayakawa
    MRG15 is a conserved chromodomain protein that associates with histone deacetylases (HDACs) and Tip60-containing histone acetyltransferase (HAT) complexes. Here we further characterize MRG15-containing complexes and show a functional link between MRG15 and histone H3K4 demethylase activity in mammalian cells. MRG15 was predominantly localized to discrete nuclear subdomains enriched for Ser2 -phosphorylated RNA polymerase II, suggesting it is involved specifically with active transcription. Protein analysis of the MRG15-containing complexes led to the identification of RBP2, a JmjC domain-containing protein. Remarkably, over-expression of RBP2 greatly reduced the H3K4 methylation in culture human cells in vivo, and recombinant RBP2 efficiently removed H3K4 methylation of histone tails in vitro. Knockdown of RBP2 resulted in increased H3K4 methylation levels within transcribed regions of active genes. Our findings demonstrate that RBP2 associated with MRG15 complex to maintain reduced H3K4 methylation at transcribed regions, which may ensure the transcriptional elongation state. [source]

    Molecular dynamics simulation on HP1 protein binding by histone H3 tail methylation and phosphorylation

    INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 4 2009
    Yan-Ke Jiang
    Abstract Trimethylation of histone H3 lysine 9 is important for recruiting heterochromatin protein 1 (HP1) to discrete regions of the genome, thereby regulating gene expression, chromatin packaging, and heterochromatin formation. Phosphorylation of histone H3 has been linked with mitotic chromatin condensation. During mitosis in vivo, H3 lysine 9 methylation and serine 10 phosphorylation can occur concomitantly on the same histone tail, whereas the influence of phosphorylation to trimethylation H3 tail recruiting HP1 remains controversial. In this work, molecular dynamics simulation of HP1 complexed with both trimethylated and phosphorylated H3 tail were performed and compared with the results from the previous methylated H3-HP1 trajectory. It is clear from the 10-ns dynamics simulation that two adjacent posttranslational modifications directly increase the flexibility of the H3 tail and weaken HP1 binding to chromatin. A combinatorial readout of two adjacent posttranslational modifications,a stable methylation and a dynamic phosphorylation mark,establish a regulatory mechanism of protein,protein interactions. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2009 [source]

    Thioredoxin interacting protein (TXNIP) induces inflammation through chromatin modification in retinal capillary endothelial cells under diabetic conditions

    JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2009
    Lorena Perrone
    Chronic hyperglycemia and activation of receptor for advanced glycation end products (RAGE) are known risk factors for microvascular disease development in diabetic retinopathy. Thioredoxin-interacting protein (TXNIP), an endogenous inhibitor of antioxidant thioredoxin (TRX), plays a causative role in diabetes and its vascular complications. Herein we investigate whether HG and RAGE induce inflammation in rat retinal endothelial cells (EC) under diabetic conditions in culture through TXNIP activation and whether epigenetic mechanisms play a role in inflammatory gene expression. We show that RAGE activation by its ligand S100B or HG treatment of retinal EC induces the expression of TXNIP and inflammatory genes such as Cox2, VEGF-A, and ICAM1. TXNIP silencing by siRNA impedes RAGE and HG effects while stable over-expression of a cDNA for human TXNIP in EC elevates inflammation. p38 MAPK-NF-,B signaling pathway and histone H3 lysine (K) nine modifications are involved in TXNIP-induced inflammation. Chromatin immunoprecipitation (ChIP) assays reveal that TXNIP over-expression in EC abolishes H3K9 tri-methylation, a marker for gene inactivation, and increases H3K9 acetylation, an indicator of gene induction, at proximal Cox2 promoter bearing the NF-,B-binding site. These findings have important implications toward understanding the molecular mechanisms of ocular inflammation and endothelial dysfunction in diabetic retinopathy. J. Cell. Physiol. 221: 262,272, 2009. © 2009 Wiley-Liss, Inc [source]

    5, flanking region of var genes nucleate histone modification patterns linked to phenotypic inheritance of virulence traits in malaria parasites

    MOLECULAR MICROBIOLOGY, Issue 6 2007
    Jose Juan Lopez-Rubio
    Summary In the human malaria parasite Plasmodium falciparum antigenic variation facilitates long-term chronic infection of the host. This is achieved by sequential expression of a single member of the 60-member var family. Here we show that the 5, flanking region nucleates epigenetic events strongly linked to the maintenance of mono-allelic var gene expression pattern during parasite proliferation. Tri- and dimethylation of histone H3 lysine 4 peak in the 5, upstream region of transcribed var and during the poised state (non-transcribed phase of var genes during the 48 h asexual life cycle), ,bookmarking' this member for re-activation at the onset of the next cycle. Histone H3 lysine 9 trimethylation acts as an antagonist to lysine 4 methylation to establish stably silent var gene states along the 5, flanking and coding region. Furthermore, we show that competition exists between H3K9 methylation and H3K9 acetylation in the 5, flanking region and that these marks contribute epigenetically to repressing or activating var gene expression. Our work points to a pivotal role of the histone methyl mark writing and reading machinery in the phenotypic inheritance of virulence traits in the malaria parasite. [source]

    Transgene-induced silencing of Arabidopsis phytochrome A gene via exonic methylation

    THE PLANT JOURNAL, Issue 6 2007
    Rekha Chawla
    Summary Transgene-induced promoter or enhancer methylation clearly retards gene activity. While exonic methylation of genes is frequently observed in the RNAi process, only sporadic evidence has demonstrated its definitive role in gene suppression. Here, we report the isolation of a transcriptionally suppressed epi-allele of the Arabidopsis thaliana phytochrome A gene (PHYA) termed phyA, that shows methylation only in symmetric CG sites resident in exonic regions. These exonic modifications confer a strong phyA mutant phenotype, characterized by elongated hypocotyls in seedlings grown under continuous far-red light. De-methylation of phyA, in the DNA methyl transferase I (met1) mutant background increased PHYA expression and restored the wild-type phenotype, confirming the pivotal role of exonic CG methylation in maintaining the altered epigenetic state. PHYA epimutation was apparently induced by a transgene locus; however, it is stably maintained following segregation. Chromatin immunoprecipitation assays revealed association with dimethyl histone H3 lysine 9 (H3K9me2), a heterochromatic marker, within the phyA, coding region. Therefore, transgene-induced exonic methylation can lead to chromatin alteration that affects gene expression, most likely through reduction in the transcription rate. [source]

    Changes in histone modification upon activation of dormant mouse blastocysts

    ANIMAL SCIENCE JOURNAL, Issue 6 2007
    Tamako MATSUHASHI
    ABSTRACT Gene expression in the implanting blastocyst is altered by stimulation with estrogen secreted from maternal ovaries. In the present study, to understand the mechanism regulating the changes in gene expression, diverse histone modifications in blastocysts were studied using a delayed implantation model, in which embryos were kept in a dormant state in the uterus by maternal ovariectomy and progesterone treatment, and then activated by injection with estrogen. Total transcriptional activity increased markedly in activated embryos, and immunocytochemistry with antibodies recognizing specific histone modifications revealed differential modification of several histones in the trophectoderm (TE) and inner cell mass (ICM) of dormant and activated embryos. High levels of histone H3 lysine 9 (H3K9) dimethylation, which suppresses gene expression, were observed in the ICM, but not in the TE, of dormant embryos, and the levels decreased when the embryos were activated, consistent with changes in transcriptional activity. Substitution of histone H3.3, a variant of H3, for dominant H3.1 increased in activated embryos, suggesting that histone substitution is involved in inducing gene expression associated with activation. In the nucleus, H3.3 was mainly localized in the nucleoli of activated embryos but not in those of dormant ones. In contrast, there were no obvious differences in the trimethylation of histone H3K9 or the acetylation of histones H3K9, H3K18 and H4K12 between dormant and activated embryos. These results suggest that a decrease in H3K9 dimethylation contributes to the acquisition of implantation competence by releasing genes from suppression. In addition, histone H3.3 substitution seems to be involved in global gene activation and facilitates the prompt recovery of dormant blastocysts to the active state by inducing rRNA synthesis, resulting in an increase in translational activity. [source]