1.Methylation and demethylation of DNA and histones in chromatin: the most complicated epigenetic marker.
Experimental & Molecular Medicine 2017;49(4):e321-
No abstract available.
Chromatin*
;
DNA*
;
Epigenomics*
;
Histones*
;
Methylation*
2.γH2AX and its application in clinical tumor research.
Ming CUI ; Yang LIU ; Guanxi WANG ; Yang LI ; Yuxin YIN
Chinese Journal of Pathology 2014;43(10):714-717
3.Building the Frequency Profile of the Core Promoter Element Patterns in the Three ChromHMM Promoter States at 200bp Intervals: A Statistical Perspective.
Heather LENT ; Kyung Eun LEE ; Hyun Seok PARK
Genomics & Informatics 2015;13(4):152-155
Recently, the Encyclopedia of DNA Elements (ENCODE) Analysis Working Group converted data from ChIP-seq analyses from the Broad Histone track into 15 corresponding chromatic maps that label sequences with different kinds of histone modifications in promoter regions. Here, we publish a frequency profile of the three ChromHMM promoter states, at 200-bp intervals, with particular reference to the existence of sequence patterns of promoter elements, GC-richness, and transcription starting sites. Through detailed and diligent analysis of promoter regions, researchers will be able to uncover new and significant information about transcription initiation and gene function.
DNA
;
Epigenomics
;
Histones
;
Promoter Regions, Genetic
4.Identification of a New Selective Chemical Inhibitor of Mutant Isocitrate Dehydrogenase-1.
Hyo Joon KIM ; Bu Young CHOI ; Young Sam KEUM
Journal of Cancer Prevention 2015;20(1):78-83
BACKGROUND: Recent genome-wide sequencing studies have identified unexpected genetic alterations in cancer. In particular, missense mutations in isocitrate dehydrogenase-1 (IDH1) at arginine 132, mostly substituted into histidine (IDH1-R132H) were observed to frequently occur in glioma patients. METHODS: We have purified recombinant IDH1 and IDH1-R132H proteins and monitored their catalytic activities. In parallel experiments, we have attempted to find new selective IDH1-R132H chemical inhibitor(s) from a fragment-based chemical library. RESULTS: We have found that IDH1, but not IDH1-R132H, can catalyze the conversion of isocitrate into alpha-ketoglutarate (alpha-KG). In addition, we have observed that IDH1-R132H was more efficient than IDH1 in converting alpha-KG into (R)-2-hydroxyglutarate (R-2HG). Moreover, we have identified a new hit molecule, e.g., 2-(3-trifluoromethylphenyl)isothioazol-3(2H)-one as a new selective IDH1-R132H inhibitor. CONCLUSIONS: We have observed an underlying biochemical mechanism explaining how a heterozygous IDH1 mutation contributes to the generation of R-2HG and increases cellular histone H3 trimethylation levels. We have also identified a novel selective IDH1-R132H chemical hit molecule, e.g., 2-(3-trifluoromethylphenyl)isothioazol-3(2H)-one, which could be used for a future lead development against IDH1-R132H.
Arginine
;
Glioma
;
Histidine
;
Histones
;
Humans
;
Mutation, Missense
5.Role of extracellular histones in liver failure.
Chinese Journal of Hepatology 2015;23(10):794-796
6.Comparison of methods for enriching urine proteins.
Hongming TENG ; Ying CUI ; Yingjie WANG ; Yue PANG ; Qingwei LI
Chinese Journal of Biotechnology 2021;37(11):4102-4110
The abundance of proteins in human urine is low and easily to be masked by high-abundance proteins during mass spectrometry analysis. Development of efficient and highly selective enrichment methods is therefore a prerequisite for achieving deep coverage of urine protein markers. Notably, different experimental methods would affect the urine protein enrichment efficacy and the coverage of urine proteome. In this study, ultrafiltration, nitrocellulose membrane enrichment and saturated ammonium sulfate precipitation were used to process 10 mL urine samples from five healthy volunteers and five bladder cancer patients. The urine proteins were enriched and separate by SDS-PAGE to compare the purification efficiency of different methods. Moreover, the peptide identification effects of different purification methods were analyzed by mass spectrometry to determine the best method for enriching urine protein histones. Saturated ammonium sulfate precipitation method outperformed the ultrafiltration and the nitrocellulose membrane enrichment methods in terms of the protein enrichment efficacy and quality. The interference of highly abundant albumin was reduced, whereas the amount of low-abundance protein was increased, and the sensitivity of mass spectrometry identification was increased. The saturated ammonium sulfate precipitation method may be applied for large-scale urine processing for screening clinical diagnostic markers through proteomics.
Histones
;
Humans
;
Mass Spectrometry
;
Proteome
;
Proteomics
;
Urinalysis
7.The Global Histone Modification Patterns of Osteosarcoma.
Sung Im DO ; Sung Jig LIM ; Youn Wha KIM ; Liliana G OLVI ; Eduardo SANTINI-ARAUJO ; Yong Koo PARK
Korean Journal of Pathology 2011;45(2):146-150
BACKGROUND: Epigenetic alteration may affect a patient's prognosis by altering the development and progression of the tumor. Some recent reports have identified a correlation between histone modification and patient outcome. However, no studies have been conducted on global histone modification in osteosarcomas. METHODS: We investigated histone modification in 54 cases of osteosarcoma by performing immunohistochemical staining. The immunohistochemical expression of four histone modification markers, acetylated H4 lysine 12 (H4K12Ac), acetylated H3 lysine 18, trimethylated H3 lysine 27, and dimethylated H3 lysine 4 were evaluated. RESULTS: High H4K12Ac expression was correlated with patient age (p=0.011). However, the other histone modification markers showed no correlation with any of the clinicopathological data such as survival, tumor grade, tumor site, metastasis, age, or gender. CONCLUSIONS: Our study showed that all four histone modification markers are expressed in osteosarcoma (median expression rate, 40 to 60%). However, we did not find a correlation with the clinicopathological factors except for age. Further study to evaluate the reason for the association between H4K12Ac and patient age is needed.
Epigenomics
;
Histones
;
Humans
;
Lysine
;
Neoplasm Metastasis
;
Osteosarcoma
;
Prognosis
8."Identification Card": Sites on Histone Modification of Cancer Cell.
Chinese Medical Sciences Journal 2015;30(4):203-209
Formation of malignant tumor originating from normal healthy cell is a multistep process including genetic and epigenetic lesions. Previous studies of cell line model systems displayed that early important epigenetic events happened in stepwise fashion prior to cell immortalization. Once these epigenetic alterations are integrated into chromatin, they will perform vertical propagation through cell subculture. Hence, status of epigenetics is dramatically important in maintaining of cell identity. Histone modification is another factor of epigenetic alterations during human oncogenesis. Histones, one of main components of chromatin, can be modified post-translationally. Histone tail modifications are regulated by corresponding modification enzymes. This review focuses on the description of relationship between the main sites of histone modification and oncogenesis.
Acetylation
;
Carcinogenesis
;
Epigenesis, Genetic
;
Histones
;
metabolism
;
Humans
;
Methylation
;
Phosphorylation
9.Dual Inhibitors Against Topoisomerases and Histone Deacetylases.
Journal of Cancer Prevention 2015;20(2):85-91
Topoisomerases and histone deacetylases (HDACs) are considered as important therapeutic targets for a wide range of cancers, due to their association with the initiation, proliferation and survival of cancer cells. Topoisomerases are involved in the cleavage and religation processes of DNA, while HDACs regulate a dynamic epigenetic modification of the lysine amino acid on various proteins. Extensive studies have been undertaken to discover small molecule inhibitor of each protein and thereby, several drugs have been transpired from this effort and successfully approved for clinical use. However, the inherent heterogeneity and multiple genetic abnormalities of cancers challenge the clinical application of these single targeted drugs. In order to overcome the limitations of a single target approach, a novel approach, simultaneously targeting topoisomerases and HDACs with a single molecule has been recently employed and attracted much attention of medicinal chemists in drug discovery. This review highlights the current studies on the discovery of dual inhibitors against topoisomerases and HDACs, provides their pharmacological aspects and advantages, and discusses the challenges and promise of the dual inhibitors.
DNA
;
Drug Discovery
;
Epigenomics
;
Histone Deacetylases*
;
Histones*
;
Lysine
;
Population Characteristics
10.Histone modifications during spermatogenesis and male infertility.
Xiao-yan PAN ; Zhi-xin LI ; Zheng-chao WANG ; Xue-nan WANG ; Bing-yang HUANG ; Zhao-hua DOU ; Yan-mei SUN
Acta Academiae Medicinae Sinicae 2014;36(1):108-113
Many pathological phenomena of male infertility are related to epigenetic changes in male germ cells. Epigenetic regulation during spermatogenesis plays an important role in mitotic/meiotic divisions and spermiogenesis. The histones have various post-translational modifications on different amino acid residues during spermatogenesis. These modifications are crucial to the precise regulation of spermatogenesis. Moreover, the histone-to-protamine transition will occur during spermiogenesis. Many studies have also found that abnormal changes of histone modifications during spermatogenesis may damage the sperm development, leading to male sterility. This article reviews the changes of histone modifications during spermatogenesis, the regulation of the development of male germ cells, and the relationship between histone abnormalities and male sterility.
Epigenesis, Genetic
;
Histones
;
metabolism
;
Humans
;
Infertility, Male
;
physiopathology
;
Male
;
Spermatogenesis