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成为或不成为(在 LAD 中):层粘连蛋白在转录调控中的新兴作用。

To be or not be (in the LAD): emerging roles of lamin proteins in transcriptional regulation.

机构信息

Universidad de Buenos Aires (UBA), Facultad de Ciencias Exactas y Naturales, Departamento de Fisiología, Biología Molecular y Celular and CONICET-UBA, Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Buenos Aires, Argentina.

出版信息

Biochem Soc Trans. 2022 Apr 29;50(2):1035-1044. doi: 10.1042/BST20210858.

DOI:10.1042/BST20210858
PMID:35437578
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9162450/
Abstract

Lamins are components of the nuclear lamina, a protein meshwork that underlies the nuclear membrane. Lamins interact with chromatin in transcriptionally silent regions defined as lamina-associated-domains (LADs). However, recent studies have shown that lamins regulate active transcription inside LADs. In addition, ChIP-seq analysis has shown that lamins interact with lamin-dependent promoters and enhancers located in the interior of the nucleus. Moreover, functional studies suggest that lamins regulate transcription at associated-promoters and long-range chromatin interactions of key developmental gene programs. This review will discuss emerging, non-canonical functions of lamins in controlling non-silent genes located both inside and outside of LADs, focusing on transcriptional regulation and chromatin organization in Drosophila and mammals as metazoan model organisms.

摘要

核纤层蛋白是核纤层的组成部分,核纤层是位于核膜下的蛋白质网格。核纤层蛋白与转录沉默区域的染色质相互作用,这些区域被定义为核纤层相关结构域(LADs)。然而,最近的研究表明,核纤层蛋白在 LADs 内调节活跃的转录。此外,ChIP-seq 分析表明,核纤层蛋白与位于核内部的依赖核纤层的启动子和增强子相互作用。此外,功能研究表明,核纤层蛋白在相关启动子和关键发育基因程序的长距离染色质相互作用中调节转录。这篇综述将讨论核纤层蛋白在控制位于 LAD 内外的非沉默基因中的新兴非经典功能,重点是在果蝇和哺乳动物作为后生动物模式生物中的转录调控和染色质组织。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa31/9162450/ee5feacc3d88/BST-50-1035-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa31/9162450/5bc94b1eebb3/BST-50-1035-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa31/9162450/ee5feacc3d88/BST-50-1035-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa31/9162450/5bc94b1eebb3/BST-50-1035-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa31/9162450/ee5feacc3d88/BST-50-1035-g0002.jpg

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Pathogenic LMNA variants disrupt cardiac lamina-chromatin interactions and de-repress alternative fate genes.
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