ABSTRACT The nuclear lamina contributes to the regulation of gene expression and to chromatin organization. Mutations in A-type nuclear lamins cause laminopathies, some of which are associated with a loss of heterochromatin at the nuclear periphery. Until recently however, little if any information has been provided on where and how lamin A interacts with the genome and on how disease-causing lamin A mutations may rearrange genome conformation. Here, we review aspects of nuclear lamin association with the genome. We highlight recent evidence of reorganization of lamin A-chromatin interactions in cellular models of laminopathies, and implications on the 3-dimensional rearrangement of chromatin in these models, including patient cells. We discuss how a hot-spot lipodystrophic lamin A mutation alters chromatin conformation and epigenetic patterns at an anti-adipogenic locus, and conclude with remarks on links between lamin A, Polycomb and the pathophysiology of laminopathies. The recent findings presented here collectively argue towards a deregulation of large-scale and local spatial genome organization by a subset of lamin A mutations causing laminopathies.

中文翻译：

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导致椎板病的 lamin A 突变重新配置了椎板相关结构域和局部空间染色质构象

摘要 核层有助于基因表达的调节和染色质组织。A 型核纤层蛋白的突变会导致椎板病，其中一些与核外围异染色质的丢失有关。然而，直到最近，关于 lamin A 与基因组相互作用的位置和方式以及致病 lamin A 突变如何重新排列基因组构象的信息几乎没有提供。在这里，我们回顾了核纤层蛋白与基因组关联的各个方面。我们强调了最近在椎板病细胞模型中重组核纤层蛋白 A-染色质相互作用的证据，以及对这些模型中染色质 3 维重排的影响，包括患者细胞。我们讨论了热点脂肪营养不良 lamin A 突变如何改变抗脂肪形成位点的染色质构象和表观遗传模式，并以对 lamin A、Polycomb 和椎板病病理生理学之间联系的评论作为结论。此处提出的最近发现共同主张通过导致椎板病的 lamin A 突变子集对大规模和局部空间基因组组织的放松管制。