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理解和工程化染色质作为一个跨越长度和时间尺度的动力学系统。

Understanding and Engineering Chromatin as a Dynamical System across Length and Timescales.

机构信息

Department of Chemical Engineering, MIT, 25 Ames St., Cambridge, MA 02139, USA.

Department of Systems Biology, Harvard Medical School, Boston, MA, USA; Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA.

出版信息

Cell Syst. 2020 Nov 18;11(5):424-448. doi: 10.1016/j.cels.2020.09.011.

Abstract

Connecting the molecular structure and function of chromatin across length and timescales remains a grand challenge to understanding and engineering cellular behaviors. Across five orders of magnitude, dynamic processes constantly reshape chromatin structures, driving spaciotemporal patterns of gene expression and cell fate. Through the interplay of structure and function, the genome operates as a highly dynamic feedback control system. Recent experimental techniques have provided increasingly detailed data that revise and augment the relatively static, hierarchical view of genomic architecture with an understanding of how dynamic processes drive organization. Here, we review how novel technologies from sequencing, imaging, and synthetic biology refine our understanding of chromatin structure and function and enable chromatin engineering. Finally, we discuss opportunities to use these tools to enhance understanding of the dynamic interrelationship of chromatin structure and function.

摘要

连接染色质的分子结构和功能跨越长度和时间尺度仍然是理解和工程细胞行为的一个巨大挑战。跨越五个数量级,动态过程不断重塑染色质结构,驱动基因表达和细胞命运的时空模式。通过结构和功能的相互作用,基因组作为一个高度动态的反馈控制系统运作。最近的实验技术提供了越来越详细的数据,这些数据修正并补充了基因组结构的相对静态的、层次化的观点,使人们了解了动态过程如何驱动组织。在这里,我们回顾了测序、成像和合成生物学等新技术如何改进我们对染色质结构和功能的理解,并使染色质工程成为可能。最后,我们讨论了利用这些工具来增强对染色质结构和功能的动态相互关系的理解的机会。

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