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核纤层:在染色体定位和基因表达中的作用。

Nuclear filaments: role in chromosomal positioning and gene expression.

机构信息

Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics , Kolkata, India.

Department of Cell Biology, Yale University School of Medicine , Connecticut, New Haven, USA.

出版信息

Nucleus. 2020 Dec;11(1):99-110. doi: 10.1080/19491034.2020.1769445.

Abstract

Nuclear lamins form an elastic meshwork underlying the inner nuclear membrane and provide mechanical rigidity to the nucleus and maintain shape. Lamins also maintain chromosome positioning and play important roles in several nuclear processes like replication, DNA damage repair, transcription, and epigenetic modifications. LMNA mutations affect cardiac tissue, muscle tissues, adipose tissues to precipitate several diseases collectively termed as laminopathies. However, the rationale behind LMNA mutations and laminopathies continues to elude scientists. During interphase, several chromosomes form inter/intrachromosomal contacts inside nucleoplasm and several chromosomal loops also stretch out to make a 'loop-cluster' which are key players to regulate gene expressions. In this perspective, we have proposed that the lamin network in tandem with nuclear actin and myosin provide mechanical rigidity to the chromosomal contacts and facilitate loop-clusters movements. LMNA mutations thus might perturb the landscape of chromosomal contacts or loop-clusters positioning which can impair gene expression profile.

摘要

核纤层蛋白形成核膜内层下的弹性网格,为细胞核提供机械刚性并维持其形状。核纤层蛋白还维持着染色体的定位,并在核内的复制、DNA 损伤修复、转录和表观遗传修饰等多个过程中发挥重要作用。LMNA 突变影响心脏组织、肌肉组织和脂肪组织,导致几种疾病的统称——核纤层病。然而,LMNA 突变和核纤层病的根本原因仍困扰着科学家们。在间期,几个染色体在核质内形成染色体间/内接触,几个染色体环也伸展形成“环簇”,这是调节基因表达的关键因素。从这个角度来看,我们提出核纤层蛋白与核肌动蛋白和肌球蛋白一起为染色体接触提供机械刚性,并促进环簇的运动。因此,LMNA 突变可能会扰乱染色体接触或环簇定位的格局,从而损害基因表达谱。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1ba/7529408/6bf368c7d466/KNCL_A_1769445_F0001_OC.jpg

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