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细胞干性中染色质组织的调控:长链非编码RNA的新作用

Regulation of Chromatin Organization in Cell Stemness: The Emerging Role of Long Non-coding RNAs.

作者信息

Dehghani Hesam

机构信息

Stem Cell Biology and Regenerative Medicine Research Group, Research Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran.

Division of Biotechnology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran.

出版信息

Stem Cell Rev Rep. 2021 Dec;17(6):2042-2053. doi: 10.1007/s12015-021-10209-8. Epub 2021 Jun 28.

Abstract

Chromatin is organized as chromosome territories in the nucleus of an interphase cell. The cell-type- and cell-state-specific organization of chromatin including the location, volume, compaction level, and spatial arrangement of chromosome territories are the major determinants of genome function. In addition, in response to different signaling stimuli and regulatory cues, it is the dynamic adaptation of chromatin structure that establishes and organizes transcriptional programs. It is known that varying levels of stemness are defined by gene regulatory networks. Accordingly, chromatin is the main milieu to host the transcriptional programs and gene regulatory networks responsible for the stemness status of a cell. In this review, our current understanding of the spatial organization of chromatin and the ways by which it defines stemness are discussed. In particular, the role of lncRNAs that regulate and affect chromatin organization and stemness properties are delineated. These roles can be categorized into the topics of specific binding to and epigenetic regulation of the promoter of pluripotency genes, their interaction with transcription factors, coordinating the intra- and inter-chromosomal looping of pluripotency-related genes, and their RNA-independent functions. This review brings together the results of studies that have begun to clarify the emerging roles of lncRNAs in the regulation of chromatin organization adapted for stemness and cancer plasticity.

摘要

染色质在间期细胞核中以染色体区域的形式存在。染色质的细胞类型和细胞状态特异性组织,包括染色体区域的位置、体积、压缩水平和空间排列,是基因组功能的主要决定因素。此外,响应不同的信号刺激和调控线索,染色质结构的动态适应建立并组织了转录程序。众所周知,不同水平的干性由基因调控网络定义。因此,染色质是承载负责细胞干性状态的转录程序和基因调控网络的主要环境。在本综述中,我们讨论了目前对染色质空间组织及其定义干性方式的理解。特别地,描述了lncRNAs在调节和影响染色质组织及干性特性方面的作用。这些作用可分为与多能性基因启动子的特异性结合和表观遗传调控、它们与转录因子的相互作用、协调多能性相关基因的染色体内和染色体间环化以及它们的RNA非依赖性功能等主题。本综述汇集了一些研究结果,这些研究开始阐明lncRNAs在调节适应干性和癌症可塑性的染色质组织中的新作用。

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