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动态染色质技术:从单个分子到细胞中的表观基因组调控。

Dynamic chromatin technologies: from individual molecules to epigenomic regulation in cells.

机构信息

Laboratoire de Biologie Moléculaire des Eucaryotes (LBME), Center for Integrative Biology (CBI), Universite Paul Sabatier Toulouse III, CNRS, Bâtiment IBCG, 31062 Toulouse, France.

Laboratory of Biophysical Chemistry of Macromolecules (LCBM), Institute of Chemical Sciences and Engineering (ISIC), École Polytechnique Fédérale de Lausanne, CH B3 485, Station 6, CH-1015 Lausanne, Switzerland.

出版信息

Nat Rev Genet. 2017 Aug;18(8):457-472. doi: 10.1038/nrg.2017.28. Epub 2017 May 22.

Abstract

The establishment and maintenance of chromatin states involves multiscale dynamic processes integrating transcription factor and multiprotein effector dynamics, cycles of chemical chromatin modifications, and chromatin structural organization. Recent developments in genomic technologies are emerging that are enabling a view beyond ensemble- and time-averaged properties and are revealing the importance of dynamic chromatin states for cell fate decisions, differentiation and reprogramming at the single-cell level. Concurrently, biochemical and single-molecule methodologies are providing key insights into the underlying molecular mechanisms. Combining results from defined in vitro and single-molecule studies with single-cell genomic approaches thus holds great promise for understanding chromatin-based transcriptional memory and cell fate. In this Review, we discuss recent developments in biochemical, single-molecule biophysical and single-cell genomic technologies and review how the findings from these approaches can be integrated to paint a comprehensive picture of dynamic chromatin states.

摘要

染色质状态的建立和维持涉及多尺度动态过程,包括转录因子和多蛋白效应子动力学、化学染色质修饰循环以及染色质结构组织。基因组技术的最新发展正在出现,这些发展正在超越整体和时间平均性质的视角,并揭示动态染色质状态对单细胞水平的细胞命运决定、分化和重编程的重要性。同时,生化和单分子方法为潜在的分子机制提供了关键的见解。因此,将定义的体外和单分子研究与单细胞基因组方法的结果相结合,对于理解基于染色质的转录记忆和细胞命运具有很大的前景。在这篇综述中,我们讨论了生化、单分子生物物理和单细胞基因组技术的最新进展,并回顾了这些方法的发现如何整合在一起,以描绘动态染色质状态的全貌。

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