东南大学 生物电子学国家重点实验室
新疆维吾尔自治区自然科学基金(2012211A076), 国家重点基础研究发展计划(973)(2012CB316501), 国家自然科学基金(31240080, 31371339)和江苏省自然科学基金(12KJD520006)资助项目
State Key Laboratory of Bioelectronics, Southeast University
chromatin, nucleosome, histone modifications, distribution mode, high throughput DNA sequencing
染色质是真核DNA的存在方式,可以通过影响DNA的可及性调节基因转录,其基本单元为核小体,系由约147 bp的DNA缠绕在组蛋白八联体上形成的结构,核小体之间以连接DNA相连.核小体组蛋白上能发生甲基化和乙酰化等化学修饰.核小体位置、DNA的甲基化和组蛋白的修饰等对染色质状态(常染色质或异染色质)及基因组之间的长程相互作用有重要影响.近年,基于高通量测序技术,核小体位置和染色质修饰在多种细胞中的基因组分布已被测定.结果显示,这些标记的分布模式具有位点特异、动态变化、相互偶联和高度复杂的特征.本文详细回顾并评述了核小体位置和染色质修饰的分布模式、对应生物学功能、修饰之间的关联、实验测定技术、染色质状态的计算分析等内容.该工作对于深入认识和理解染色质的表观遗传调节机制有重要意义.
Chromatin packages eukaryotic DNA, it can affect accessibility of DNA, thus chromatin has important roles in gene transcription regulation, DNA replication, DNA repair, and so on. The basic unit of chromatin is nucleosome consisting of ~147 DNA which sharply bends and tightly wraps on surface of octamer of histones. Between two nucleosomes is linker DNA. Histones can be modified by methylation and acetylation. Chromatin state (euchromatin and heterochromatin) is determined by the combinatorial effects of nucleosome positioning, histone modifications, and chromatin-binding proteins. Recently, by virtue of high throughput sequencing technique, the distributions of the chromatin marks were genome-widely determined in various cells. Results indicated that the distribution mode is specific at key sites of genome and is dynamically changed with both cell types and environment stimulus, showing a complex plot. In this paper, we detailedly reviewed the distribution modes of chromatin marks, biological meanings of the modes, interactions of the chromatin marks (nucleosome, DNA and histone modifications, histone variants, chromatin-binding proteins), techniques that were used to determine the marks, and the computational analysis for chromatin states. This work is important in understanding epigenetic regulation mechanism.
刘宏德,罗 坤,马 昕,翟金城,谢建明,孙 啸,万亚坤.核小体及染色质修饰的基因组分布模式和染色质状态[J].生物化学与生物物理进展,2013,40(11):1088-1099
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