共查询到20条相似文献,搜索用时 0 毫秒
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M A Martinez-Balbás A J Bannister K Martin P Haus-Seuffert M Meisterernst T Kouzarides 《The EMBO journal》1998,17(10):2886-2893
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The abnormal accumulation of Cu2+ is closely correlated with the incidence of different diseases, such as Alzheimer's disease and Wilson disease. To study in vivo functions of Cu2+ will lead to a better understanding of the nature of these diseases. In the present study, effect of Cu2+ on histone acetylation was investigated in human hepatoma cells. Exposure of cells to Cu2+ resulted in a significant decrease of histone acetylation, as indicated by the decrease of the overall histone acetylation and the decrease of histone H3 and H4 acetylation. Since histone acetyltransferase (HAT) and histone deacetylase (HDAC) are the enzymes controlled the state of histone acetylation in vivo, we tested their contribution to the inhibition of Cu2+ on histone acetylation. One hundred nanomolar trichostatin A, the specific inhibitor of HDAC, did not attenuate the inhibitory effect of Cu2+ on histone acetylation. Combined with that Cu2+ showed no effect on the in vitro activity of HDAC, these results led to the conclusion that it is HAT, but not HDAC that is involved in Cu2+ -induced histone hypoacetylation. This conclusion was confirmed by the facts that (1) Cu2+ significantly inhibited the in vitro activity of HAT, (2) Cu2+ -treated cells possessed a lower HAT activity than control cells, and (3) 50 or 100 microM bathocuproine disulfonate, a chelator of Cu2+, significantly attenuated the inhibition of Cu2+ on HAT activity and histone acetylation in the similar pattern. Combined with that Cu2+ showed no or obvious cytotoxicity at 100 or 200 microM in human hepatoma cells, and the previous study that Cu2+ inhibits the histone H4 acetylation of yeast cells at nontoxic or toxic levels, the data presented here suggest that inhibiting histone acetylation is probably one general in vivo function of Cu2+, where HAT is its molecular target. 相似文献
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Interest in histone acetylation has risen dramatically in recent years. In the following report, we present methods for the analysis of histone acetyltransferase activity in vitro. Protocols are described for radiolabeling histone proteins and N-terminal "tail" peptides, and for the analysis of acetylation by immunoblotting. Techniques for acetylating immobilized histone peptides are also described. 相似文献
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Anderson de Mendona Amarante Isabel Caetano de Abreu da Silva Vitor Coutinho Carneiro Amanda Roberta Revoredo Vicentino Marcia de Amorim Pinto Luiza Mendona Higa Kanhu Charan Moharana Octavio A. C. Talyuli Thiago Motta Venancio Pedro Lagerblad de Oliveira Marcelo Rosado Fantappi 《PLoS neglected tropical diseases》2022,16(6)
Epigenetic mechanisms are responsible for a wide range of biological phenomena in insects, controlling embryonic development, growth, aging and nutrition. Despite this, the role of epigenetics in shaping insect-pathogen interactions has received little attention. Gene expression in eukaryotes is regulated by histone acetylation/deacetylation, an epigenetic process mediated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). In this study, we explored the role of the Aedes aegypti histone acetyltransferase CBP (AaCBP) after infection with Zika virus (ZIKV), focusing on the two main immune tissues, the midgut and fat body. We showed that the expression and activity of AaCBP could be positively modulated by blood meal and ZIKV infection. Nevertheless, Zika-infected mosquitoes that were silenced for AaCBP revealed a significant reduction in the acetylation of H3K27 (CBP target marker), followed by downmodulation of the expression of immune genes, higher titers of ZIKV and lower survival rates. Importantly, in Zika-infected mosquitoes that were treated with sodium butyrate, a histone deacetylase inhibitor, their capacity to fight virus infection was rescued. Our data point to a direct correlation among histone hyperacetylation by AaCBP, upregulation of antimicrobial peptide genes and increased survival of Zika-infected-A. aegypti. 相似文献
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Structure and chemistry of the p300/CBP and Rtt109 histone acetyltransferases: implications for histone acetyltransferase evolution and function 总被引:1,自引:0,他引:1
The recent structure and associated biochemical studies of the metazoan-specific p300/CBP and fungal-specific Rtt109 histone acetyltransferases (HATs) have provided new insights into the ancestral relationship between HATs and their functions. These studies point to a common HAT ancester that has evolved around a common structural framework to form HATs with divergent catalytic and substrate-binding properties. These studies also point to the importance of regulatory loops within HATs and autoacetylation in HAT function. Implications for future studies are discussed. 相似文献
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Gusterson RJ Jazrawi E Adcock IM Latchman DS 《The Journal of biological chemistry》2003,278(9):6838-6847
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The diverse functions of histone acetyltransferase complexes 总被引:31,自引:0,他引:31
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A pronounced transitory increase of histone acetyltransferase (EC 2.3.1.48) activity before the onset of DNA replication is shown to occur in regenerating rat liver. This effect is followed by an increase in the H1/H1(0) ratio at the start of DNA synthesis; H1(0) de is replaced by H1. Histone acetylation and H1/H1(0) exchange are discussed as steps in the signal transduction for DNA replication. 相似文献
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A simple radiometric assay for histone acetyltransferase (HAT) activity employing a PhosphorImager is described. In the proposed procedure, following incubation of [1-14C]acetyl coenzyme A (CoA), histones, and HAT enzyme, radiolabeled histones are fixed on GF/F glass microfiber filter while the excess of acetyl CoA is washed out. Afterward, the filter is exposed to a phosphor-screen and the resulting spot signals are quantified with a PhosphorImager. Given the small volumes required, the new assay reduces reagent consumption and contaminated waste. Moreover, the assay can be performed with a large number of samples simultaneously, is applicable on different protein substrates, and is adaptable to the analysis of other protein modifications. 相似文献
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Natalya Voloshchuk Anita Y. Zhu David Snydacker Jin Kim Montclare 《Bioorganic & medicinal chemistry letters》2009,19(18):5449-5451
To explore the impact of global incorporation of fluorinated aromatic amino acids on protein function, we investigated the effects of three monofluorinated phenylalanine analogs para-fluorophenylalanine (pFF), meta-fluorophenylalanine (mFF), and ortho-fluorophenylalanine (oFF) on the stability and enzymatic activity of the histone acetyltransferase (HAT), tGCN5. We selected this set of fluorinated amino acids because they bear the same size and overall polarity but alter in side chain shape and dipole direction. Our experiments showed that among three fluorinated amino acids, the global incorporation of pFF affords the smallest perturbation to the structure and function of tGCN5. 相似文献