Nuclear filaments: role in chromosomal positioning and gene expression.

Manindra Bera, Kaushik Sengupta
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引用次数: 10

Abstract

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.

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核丝:在染色体定位和基因表达中的作用。
核层蛋白在核膜下形成弹性网,为细胞核提供机械刚性并保持形状。层粘连蛋白还维持染色体定位,并在复制、DNA损伤修复、转录和表观遗传修饰等核过程中发挥重要作用。LMNA突变影响心脏组织,肌肉组织,脂肪组织沉淀几种疾病统称为椎板病。然而,科学家们仍然不清楚LMNA突变和椎板病背后的原理。在间期,若干染色体在核质内形成染色体间/染色体内接触,若干染色体环也伸展形成“环簇”,这是调节基因表达的关键角色。从这个角度来看,我们提出了核肌动蛋白和肌凝蛋白串联的纤层蛋白网络为染色体接触提供了机械刚性,并促进了环簇运动。因此,LMNA突变可能会扰乱染色体接触或环簇定位,从而损害基因表达谱。
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