The role of lamin B1 for the maintenance of nuclear structure and function

The role of lamin B1 for the maintenance of nuclear structure and function
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DOI:
10.1080/19491034.2014.1003510
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发表时间:
2015-01-01
期刊:
影响因子:
3.7
通讯作者:
Ried, Thomas
Ried, Thomas
中科院分区:
生物学2区
文献类型:
--
作者:
Camps, Jordi;Erdos, Michael R.;Ried, Thomas

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核纤层蛋白构成核纤层的整体结构组分。然而,它们对染色体区域的结构和稳定性以及对基因表达调控的影响在较小程度上被探索。通过3D-FISH,Camps及其同事表明,核纤层蛋白B1(LMNB 1)是间期核中正确的染色体凝聚所必需的,LMNB 1的缺乏会触发兼性异染色质的表观遗传标记H3 K27 me 3向核内部的重新定位。此外,LMNB 1抑制由于S期延迟和增加的基因组不稳定性而减缓细胞生长。最后,沉默LMNB 1导致扩大核斑点和多个基因的选择性剪接的广泛变化。总之,这些数据表明LMNB 1在染色体区域的浓缩、异染色质的分布以及基因表达和剪接的调节中起着核心作用。
Lamins constitute an integral structural component of the nuclear lamina. However, their impact on the structure and stability of chromosome territories, and on the regulation of gene expression is explored to a lesser extent. By 3D-FISH, Camps and colleagues showed that lamin B1 (LMNB1) is required for proper chromosome condensation in interphase nuclei, and deficiency of LMNB1 triggers the relocation of the epigenetic mark of facultative heterochromatin, H3K27me3, toward the interior of the nucleus. Additionally, LMNB1 repression slowed cellular growth due to S-phase delays and increased genomic instability. Finally, silencing of LMNB1 resulted in enlarged nuclear speckles and in extensive changes in alternative splicing of multiple genes. Altogether, the data suggest a central role of LMNB1 for the condensation of chromosome territories, for the distribution of heterochromatin, and for the regulation of gene expression and splicing.