ABSTRACT The alteration of the several roles that Lamin A/C plays in the mammalian cell leads to a broad spectrum of pathologies that – all together – are named laminopathies. Among those, the Emery Dreifuss Muscular Dystrophy (EDMD) is of particular interest as, despite the several known mutations of Lamin A/C, the genotype–phenotype correlation still remains poorly understood; this suggests that the epigenetic background of patients might play an important role during the time course of the disease. Historically, both a mechanical role of Lamin A/C and a regulative one have been suggested as the driving force of laminopathies; however, those two hypotheses are not mutually exclusive. Recent scientific evidence shows that Lamin A/C sustains the correct gene expression at the epigenetic level thanks to the Lamina Associated Domains (LADs) reorganization and the crosstalk with the Polycomb Group of Proteins (PcG). Furthermore, the PcG-dependent histone mark H3K27me3 increases under mechanical stress, finally pointing out the link between the mechano-properties of the nuclear lamina and epigenetics. Here, we summarize the emerging mechanisms that could explain the high variability seen in Emery Dreifuss muscular dystrophy.

中文翻译：

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Emery Dreifuss Muscular Dystrophy 中的机械转导、核结构和表观遗传学

摘要 Lamin A/C 在哺乳动物细胞中扮演的几个角色的改变导致了广泛的病理，这些病理统统统称为 laminopathies。其中，Emery Dreifuss Muscular Dystrophy (EDMD) 尤其令人感兴趣，因为尽管 Lamin A/C 有几个已知的突变，但基因型 - 表型相关性仍然知之甚少；这表明患者的表观遗传背景可能在疾病的时间过程中发挥重要作用。从历史上看，Lamin A/C 的机械作用和调节作用都被认为是椎板病的驱动力。然而，这两种假设并不相互排斥。最近的科学证据表明，由于薄层相关结构域 (LAD) 重组和与多梳蛋白组 (PcG) 的串扰，Lamin A/C 在表观遗传水平上维持正确的基因表达。此外，PcG 依赖性组蛋白标记 H3K27me3 在机械应力下增加，最终指出核层的机械特性与表观遗传学之间的联系。在这里，我们总结了可以解释 Emery Dreifuss 肌营养不良症高变异性的新兴机制。