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Comparative Epigenetic Analyses of Acute and Chronic Leukemia  [PDF]
Yan Zhang, Dianjing Guo
Journal of Biosciences and Medicines (JBM) , 2015, DOI: 10.4236/jbm.2015.36005
Abstract:

Comparative analysis of epigenetic alterations between acute vs. chronic leukemia, with an emphasis on histone modifications, was conducted. We focus on the promoter regions of the whole genomes as well as oncogenes. Our results revealed that obvious differential histone modifications pattern exists between the two subtypes. H3K27ac has a high tag density in the promoter region in both Dnd41 cell lines and K562 cell lines. H3K27ac and H3K4me1 have high correlation between the two cell lines of oncogenes. Similar results were also achieved in the promoter region of high expression genes in the Jurkat and K562 cell lines based on RNA-seq data. This suggests that H2K27ac and H3K4me1 are active regulators in leukemia cell lines.

Comparative Epigenetics Analyses of Acute and Chronic Leukemia  [PDF]
Zhang Yan, Dianjing Guo
Journal of Biosciences and Medicines (JBM) , 2015, DOI: 10.4236/jbm.2015.37002
Abstract: Comparative analysis of epigenetic alterations between acute and chronic leukemia, with an emphasis on histone modifications, was conducted. We focused on the promoter regions of the whole genomes as well as oncogenes. Our results revealed that obvious differential histone modifications pattern existed between the two subtypes. H3K27ac had a high tag density in the promoter region in both Dnd41 cell lines and K562 cell lines. H3K27ac and H3K4me1 had high correlation between the two cell lines of oncogenes. Similar results were also achieved in the promoter region of high expression genes in the Jurkat and K562 cell lines based on RNA-seq data. This suggested that H2K27ac and H3K4me1 were active regulators in leukemia cell lines.
Induction of Apoptosis and Acetylation of Histone H3 and H4 by Arctigenin in the Human Melanoma Cell Line SK-MEL-28  [PDF]
Jin Boo Jeong, Se Chul Hong, Jin Suk Koo, Hyung Jin Jeong
Food and Nutrition Sciences (FNS) , 2011, DOI: 10.4236/fns.2011.22018
Abstract: Cutaneous melanoma is one of the most aggressive forms of skin cancer. Arctigenin, one of the major bioactive compo-nents of Arctii Fructus, has been reported to exhibit antioxidant, antitumor and anti-inflammatory activities. In the pre-sent study, we investigated the effect of arctigenin on induction of apoptosis in highly metastatic SK-MEL-28 human melanoma cells. Arctigenin inhibited growth of SK-MEL-28 cells in a dose-dependent manner. Treatment of SK-MEL-28cells with arctigenin caused cleavage of caspases 3, 7 and 9, and poly (ADP-ribose) polymerase in a dose-dependent manner. Furthermore, acetylation of histone H3 and H4 in the SK-MEL-28 cells was dramatically increased by arctigenin treatment. Collectively, these findings indicate that arctigenin-induces apoptosis of SK-MEL-28 melanoma cells via activation of caspases and histone acetylation.
The Role of Bromodomain Proteins in Regulating Gene Expression
Gabrielle A. Josling,Shamista A. Selvarajah,Michaela Petter,Michael F. Duffy
Genes , 2012, DOI: 10.3390/genes3020320
Abstract: Histone modifications are important in regulating gene expression in eukaryotes. Of the numerous histone modifications which have been identified, acetylation is one of the best characterised and is generally associated with active genes. Histone acetylation can directly affect chromatin structure by neutralising charges on the histone tail, and can also function as a binding site for proteins which can directly or indirectly regulate transcription. Bromodomains specifically bind to acetylated lysine residues on histone tails, and bromodomain proteins play an important role in anchoring the complexes of which they are a part to acetylated chromatin. Bromodomain proteins are involved in a diverse range of functions, such as acetylating histones, remodeling chromatin, and recruiting other factors necessary for transcription. These proteins thus play a critical role in the regulation of transcription.
Acetate supplementation modulates brain histone acetylation and decreases interleukin-1β expression in a rat model of neuroinflammation
Mahmoud L Soliman, Mark D Smith, Heidi M Houdek, Thad A Rosenberger
Journal of Neuroinflammation , 2012, DOI: 10.1186/1742-2094-9-51
Abstract: In this study, we examined the effect of a 28-day-dosing regimen of glyceryl triacetate, to induce acetate supplementation, on brain histone acetylation and interleukin-1β expression in a rat model of lipopolysaccharide-induced neuroinflammation. The effect was analyzed using Western blot analysis, quantitative real-time polymerase chain reaction and enzymic histone deacetylase and histone acetyltransferase assays. Statistical analysis was performed using one-way analysis of variance, parametric or nonparametric when appropriate, followed by Tukey's or Dunn's post-hoc test, respectively.We found that long-term acetate supplementation increased the proportion of brain histone H3 acetylated at lysine 9 (H3K9), histone H4 acetylated at lysine 8 and histone H4 acetylated at lysine 16. However, unlike a single dose of glyceryl triacetate, long-term treatment increased histone acetyltransferase activity and had no effect on histone deacetylase activity, with variable effects on brain histone deacetylase class I and II expression. In agreement with this hypothesis, neuroinflammation reduced the proportion of brain H3K9 acetylation by 50%, which was effectively reversed with acetate supplementation. Further, in rats subjected to lipopolysaccharide-induced neuroinflammation, the pro-inflammatory cytokine interleukin-1β protein and mRNA levels were increased by 1.3- and 10-fold, respectively, and acetate supplementation reduced this expression to control levels.Based on these results, we conclude that dietary acetate supplementation attenuates neuroglial activation by effectively reducing pro-inflammatory cytokine expression by a mechanism that may involve a distinct site-specific pattern of histone acetylation and histone deacetylase expression in the brain.Reversible epigenetic changes play a major role in regulating gene expression in the post-mitotic brain. The most prominent mechanism involved in this process is the alteration in histone acetylation, which is known to in
Epigenetic regulation: methylation of histone and non-histone proteins
Fei Lan,Yang Shi
Science China Life Sciences , 2009, DOI: 10.1007/s11427-009-0054-z
Abstract: Histone methylation is believed to play important roles in epigenetic memory in various biological processes. However, questions like whether the methylation marks themselves are faithfully transmitted into daughter cells and through what mechanisms are currently under active investigation. Previously, methylation was considered to be irreversible, but the recent discovery of histone lysine demethylases revealed a dynamic nature of histone methylation regulation on four of the main sites of methylation on histone H3 and H4 tails (H3K4, H3K9, H3K27 and H3K36). Even so, it is still unclear whether demethylases specific for the remaining two sites, H3K79 and H4K20, exist. Furthermore, besides histone proteins, the lysine methylation and demethylation also occur on non-histone proteins, which are probably subjected to similar regulation as histones. This review discusses recent progresses in protein lysine methylation regulation focusing on the above topics, while referring readers to a number of recent reviews for the biochemistry and biology of these enzymes
Epigenetic regulation: methylation of histone and non-histone proteins

Fei Lan,Yang Shi,

中国科学C辑(英文版) , 2009,
Abstract: Histone methylation is believed to play important roles in epigenetic memory in various biological processes. However, questions like whether the methylation marks themselves are faithfully transmitted into daughter cells and through what mechanisms are currently under active investigation. Previously, methylation was considered to be irreversible, but the recent discovery of histone lysine demethylases revealed a dynamic nature of histone methylation regulation on four of the main sites of methylation on histone H3 and H4 tails (H3K4, H3K9, H3K27 and H3K36). Even so, it is still unclear whether demethylases specific for the remaining two sites, H3K79 and H4K20, exist. Furthermore, besides histone proteins, the lysine methylation and demethylation also occur on non-histone proteins, which are probably subjected to similar regulation as histones. This review discusses recent progresses in protein lysine methylation regulation focusing on the above topics, while referring readers to a number of recent reviews for the biochemistry and biology of these enzymes
The conformation alteration of mouse hepatic histones after reacting with nicotinein vitro
Xiaohong Wu,Hongfang Sun,Yuanfang Liu
Chinese Science Bulletin , 2000, DOI: 10.1007/BF02887411
Abstract: UV differential spectroscopy, fluorescence spectroscopy and circular dichroism (CD) spectroscopy assays have been applied to studying the conformation alteration of mouse hepatic histones H1 and H3 after reacting with nicotinein vitro. The results indicate that their conformation changes from regular form to random form with the increasing reaction dose of nicotine. The adduction of nicotine or its metabolites with histones H1 and H3 accounts for the conformation alteration. Nicotine may affect the structure, function and expression of genes of chromosome by changing the conformation of histones.
An in vitro assay to study the recruitment and substrate specificity of chromatin modifying enzymes
Vermeulen Michiel,Stunnenberg Hendrik G.
Biological Procedures Online , 2004, DOI: 10.1251/bpo85
Abstract: Post-translational modifications of core histones play an important role in regulating fundamental biological processes such as DNA repair, transcription and replication. In this paper, we describe a novel assay that allows sequential targeting of distinct histone modifying enzymes to immobilized nucleosomal templates using recombinant chimeric targeting molecules. The assay can be used to study the histone substrate specificity of chromatin modifying enzymes as well as whether and how certain enzymes affect each other's histone modifying activities. As such the assay can help to understand how a certain histone code is established and interpreted.
Chromatin modifications and the DNA damage response to ionizing radiation
Rakesh Kumar,Nobuo Horikoshi,Hari S. Misra,Tej K. Pandita
Frontiers in Oncology , 2013, DOI: 10.3389/fonc.2012.00214
Abstract: In order to survive, cells have evolved highly effective repair mechanisms to deal with the potentially lethal DNA damage produced by exposure to endogenous as well as exogenous agents. Ionizing radiation exposure induces highly lethal DNA damage, especially DNA double-strand breaks (DSBs), that is sensed by the cellular machinery and then subsequently repaired by either of two different DSB repair mechanisms: (1) non-homologous end joining, which re-ligates the broken ends of the DNA and (2) homologous recombination, that employs an undamaged identical DNA sequence as a template, to maintain the fidelity of DNA repair. Repair of DSBs must occur within the natural context of the cellular DNA which, along with specific proteins, is organized to form chromatin, the overall structure of which can impede DNA damage site access by repair proteins. The chromatin complex is a dynamic structure and is known to change as required for ongoing cellular processes such as gene transcription or DNA replication. Similarly, during the process of DNA damage sensing and repair, chromatin needs to undergo several changes in order to facilitate accessibility of the repair machinery. Cells utilize several factors to modify the chromatin in order to locally open up the structure to reveal the underlying DNA sequence but post-translational modification of the histone components is one of the primary mechanisms. In this review, we will summarize chromatin modifications by the respective chromatin modifying factors that occur during the DNA damage response.
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