DNA methylation topology: potential of a chromatin landmark for epigenetic drug toxicology.
DNA methylation topology: potential of a chromatin landmark for epigenetic drug toxicology.
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DOI：
10.2217/epi.11.101
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发表时间：
2011-12
期刊：
影响因子：
3.8
通讯作者：
Tajbakhsh J
中科院分区：
文献类型：
--
作者：
Tajbakhsh J
通过表观遗传药物治疗靶向染色质及其基本成分已成为治疗复杂疾病的日益关注的焦点。这种推动需要实施高通量的基于细胞的检测，利用对表观遗传机制及其干预措施的不断增长的知识来进行表观遗传药物的遗传毒性测试。 3D 定量 DNA 甲基化成像是一种新方法，通过分析荧光可视化并通过机器学习算法处理的甲基胞嘧啶和 gDNA 的差异核分布模式来检测细胞中药物诱导的 DNA 去甲基化和并发异染色质解缩/重组。利用 3D DNA 甲基化模式是一系列完全自动化测定的强大先驱，这些测定采用染色质结构和更高的组织作为各种表观遗传药物作用的新型药效生物标志物。
Targeting chromatin and its basic components through epigenetic drug therapy has become an increased focus in the treatment of complex diseases. This boost calls for the implementation of high-throughput cell-based assays that exploit the increasing knowledge about epigenetic mechanisms and their interventions for genotoxicity testing of epigenetic drugs. 3D quantitative DNA methylation imaging is a novel approach for detecting drug-induced DNA demethylation and concurrent heterochromatin decondensation/reorganization in cells through the analysis of differential nuclear distribution patterns of methylcytosine and gDNA visualized by fluorescence and processed by machine-learning algorithms. Utilizing 3D DNA methylation patterns is a powerful precursor to a series of fully automatable assays that employ chromatin structure and higher organization as novel pharmacodynamic biomarkers for various epigenetic drug actions.