排序方式： 共有22条查询结果，搜索用时 15 毫秒
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Julie E. Bolding Alexander L. Nielsen Iben Jensen Tobias N. Hansen Line A. Ryberg Samuel T. Jameson Pernille Harris Günther H. J. Peters John M. Denu Joseph M. Rogers Christian A. Olsen 《Angewandte Chemie (International ed. in English)》2023,62(49):e202314597
The sirtuins are NAD+-dependent lysine deacylases, comprising seven isoforms (SIRT1–7) in humans, which are involved in the regulation of a plethora of biological processes, including gene expression and metabolism. The sirtuins share a common hydrolytic mechanism but display preferences for different ϵ-N-acyllysine substrates. SIRT7 deacetylates targets in nuclei and nucleoli but remains one of the lesser studied of the seven isoforms, in part due to a lack of chemical tools to specifically probe SIRT7 activity. Here we expressed SIRT7 and, using small-angle X-ray scattering, reveal SIRT7 to be a monomeric enzyme with a low degree of globular flexibility in solution. We developed a fluorogenic assay for investigation of the substrate preferences of SIRT7 and to evaluate compounds that modulate its activity. We report several mechanism-based SIRT7 inhibitors as well as de novo cyclic peptide inhibitors selected from mRNA-display library screening that exhibit selectivity for SIRT7 over other sirtuin isoforms, stabilize SIRT7 in cells, and cause an increase in the acetylation of H3 K18. 相似文献
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miRNA has recently emerged as a potential biomarker for breast cancer. Even though many studies have identified ethnic variation affecting miRNA regulation, the effect of cancer stage within specific ethnicities on miRNA epigenetic remains unclear. The present study is designed to investigate miRNA regulation from two distinct ethnicities in specific cancer stages (non-Hispanic white and non-Hispanic black) using the TCGA dataset. Differentially expressed miRNAs were calculated by using the edgeR package. miRNAs with the highest or lowest log fold Change from each cancer stage were selected as a potential biomarker. miRNA-gene interaction was analyzed by using spearman correlation analysis, CLUEGO, and DIANA-mirpath. The association of biomarker candidates with diagnostic and prognostic performance was assessed using ROC and Kaplan-Meier survival analysis. miRNA-gene interaction analysis revealed the involvement of selected miRNAs in cancer progression. From eleven selected aberrant miRNAs, four of the miRNAs (hsa-mir-495, hsa-mir-592, hsa-mir-6501, and hsa-mir-937) are significantly detrimental to breast cancer diagnosis and prognosis. Hence, our result provides valuable information to explore miRNA’s role in each cancer stage between non-Hispanic white and non-Hispanic black. 相似文献
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Simon Goedecke Jörg Mühlisch Georg Hempel Michael C. Frühwald Bernhard Wünsch 《Electrophoresis》2015,36(23):2939-2950
Along with histone modifications, RNA interference and delayed replication timing, DNA methylation belongs to the key processes in epigenetic regulation of gene expression. Therefore, reliable information about the methylation level of particular DNA fragments is of major interest. Herein the methylation level at two positions of the promoter region of the gene methylguanine‐O6‐DNA‐Methyltransferase (MGMT) was investigated. Previously, it was demonstrated that the epigenetic status of this DNA region correlates with response to alkylating anticancer agents. An automated CGE method with LIF detection was established to separate the six DNA fragments resulting from combined bisulfite restriction analysis of the methylated and non‐methylated MGMT promoter. In COBRA, the DNA was treated with bisulfite converting cytosine into uracil. During PCR uracil pairs with adenine, which changes the original recognition site of the restriction enzyme Taql. Artificial probes generated by mixing appropriate amounts of DNA after bisulfite treatment and PCR amplification were used for validation of the method. The methylation levels of these samples could be determined with high accuracy and precision. DNA samples prepared by mixing the corresponding clones first and then performing PCR amplification led to non‐linear correlation between the corrected peak areas and the methylation levels. This effect is explained by slightly different PCR amplification of DNA with different sequences present in the mixture. The superiority of CGE over PAGE was clearly demonstrated. Finally, the established method was used to analyze the methylation levels of human brain tumor tissue samples. 相似文献
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Yang Feng;Sheng-Jun Chen;Bi-Feng Yuan; 《中国化学》2024,42(6):645-651
5-Methylcytosine (5mC) is a dynamic and reversible epigenetic modification in genomic DNA of higher eukaryotes. It has been well-established that the demethylation of 5mC occurs through the ten-eleven translocation (TET)-mediated oxidation of 5mC followed by thymine DNA glycosylase (TDG)-initiated base excision repair (BER). Recent findings also have identified an alternative pathway of DNA demethylation. In this pathway, TET enzymes directly oxidize 5mC to form 5-formylcytosine (5fC) or 5-carboxylcytosine (5caC). These modified bases can undergo direct deformylation or decarboxylation, respectively. Additionally, DNA demethylation can also occur through the deamination of 5mC and 5hmC, resulting in the production of thymine and 5-hydroxymethyluracil (5hmU), respectively. Various DNA demethylation pathways possess critical functional implications and roles in biological processes. This Recent Advances article will focus on the studies of mechanisms and biological functions of DNA demethylation, shedding light on the reversible nature of the epigenetic modification of 5mC. 相似文献
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Bethany Searle Dr. Markus Müller Prof. Dr. Thomas Carell Prof. Dr. Andrew Kellett 《Angewandte Chemie (International ed. in English)》2023,62(14):e202215704
The discovery of epigenetic bases has revolutionised the understanding of disease and development. Among the most studied epigenetic marks are cytosines covalently modified at the 5 position. In order to gain insight into their biological significance, the ability to determine their spatiotemporal distribution within the genome is essential. Techniques for sequencing on “next-generation” platforms often involve harsh chemical treatments leading to sample degradation. Third-generation sequencing promises to further revolutionise the field by providing long reads, enabling coverage of highly repetitive regions of the genome or structural variants considered unmappable by next generation sequencing technology. While the ability of third-generation platforms to directly detect epigenetic modifications is continuously improving, at present chemical or enzymatic derivatisation presents the most convenient means of enhancing reliability. This Review presents techniques available for the detection of cytosine modifications on third-generation platforms. 相似文献
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Xiao-Mei Shi Yi-Tong Xu Bing Wang Zheng Li Si-Yuan Yu Hang Dong Prof. Dr. Wei-Wei Zhao Prof. Dr. Dechen Jiang Prof. Hong-Yuan Chen Prof. Dr. Jing-Juan Xu 《Angewandte Chemie (International ed. in English)》2023,62(29):e202302930
Single-cell epigenetics is envisioned to decipher manifold epigenetic phenomena and to contribute to our accurate knowledge about basic epigenetic mechanisms. Engineered nanopipette technology has gained momentum in single-cell studies; however, solutions to epigenetic questions remain unachieved. This study addresses the challenge by exploring N6-methyladenine (m6A)-bearing deoxyribozyme (DNAzyme) confined within a nanopipette for profiling a representative m6A-modifying enzyme, fat mass and obesity-associated protein (FTO). Electroosmotic intracellular extraction of FTO could remove the m6A and cause DNAzyme cleavage, leading to the altered ionic current signal. Because the cleavage can release a DNA sequence, we simultaneously program it as an antisense strand against FTO-mRNA, intracellular injection of which has been shown to induce early stage apoptosis. This nanotool thus features the dual functions of studying single-cell epigenetics and programmable gene regulation. 相似文献
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Quentin T. Gauthier Sohee Cho Justin H. Carmel Bruce R. McCord 《Electrophoresis》2019,40(18-19):2565-2574
The goal of this study is to develop an epigenetic multiplex for body fluid identification based on tissue specific DNA methylation. A series of genetic loci capable of discerning the origin of DNA as coming from saliva, blood, vaginal epithelia, or semen were used for this application. The markers – BCAS4, CG06379435, VE_8, and ZC3H12D – were amplified together and then sequenced via pyrosequencing. Methylation values for cytosine guanine dinucleotide (CpG) sites at each locus were then measured across the four markers. In total, 124 samples were collected, and bisulfite modified to convert unmethylated DNA to uracil. This converted DNA was then amplified via multiplex PCR with reverse primers containing a biotin molecule. Biotinylated PCR products were then analyzed using pyrosequencing to generate a series of pyrograms containing 18 CpG sites. The percent methylation at each CpG site was determined, and then agglomerative hierarchical cluster analysis was used to create a model to indicate sample origin. Further analysis reduced the number of CpG sites required for optimal determination of body fluid type to five. This study demonstrates an efficient multiplexed body fluid identification process utilizing DNA methylation that can be easily implemented in forensic laboratories. 相似文献
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