A-type lamins form a filamentous meshwork beneath the nuclear membrane that anchors large heterochromatic genomic regions at the nuclear periphery. A-type lamins also exist as a dynamic, non-filamentous pool in the nuclear interior, where they interact with lamin-associated polypeptide 2 alpha (LAP2α). Both proteins associate with largely overlapping euchromatic genomic regions in the nucleoplasm, but the functional significance of this interaction is poorly understood. Here, we report that LAP2α relocates towards regions containing myogenic genes in the early stages of muscle differentiation, possibly facilitating efficient gene regulation, while lamins A and C mostly associate with genomic regions away from these genes. Strikingly, upon depletion of LAP2α, A-type lamins spread across active chromatin and accumulate at regions of active H3K27ac and H3K4me3 histone marks in the vicinity of myogenic genes whose expression is impaired in the absence of LAP2α. Reorganization of A-type lamins on chromatin is accompanied by depletion of the active chromatin mark H3K27ac and a significantly impaired myogenic differentiation. Thus, the interplay of LAP2α and A-type lamins is crucial for proper positioning of intranuclear lamin A/C on chromatin to allow efficient myogenic differentiation.

中文翻译：

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LAP2alpha 通过阻止核质层粘连蛋白 A/C 扩散到活性染色质区域来促进生肌基因表达


A 型核纤层蛋白在核膜下形成丝状网状结构，将大型异色性基因组区域锚定在核外围。A 型核纤层蛋白也以动态的非丝状池的形式存在于核内，它们在那里与核纤层蛋白相关多肽 2 α （LAP2α） 相互作用。这两种蛋白质都与核质中基本重叠的常染色质基因组区域相关，但这种相互作用的功能意义知之甚少。在这里，我们报道了 LAP2α 在肌肉分化的早期阶段重新定位到包含生肌基因的区域，可能促进了有效的基因调控，而层粘连蛋白 A 和 C 主要与远离这些基因的基因组区域相关。引人注目的是，在 LAP2α 耗尽后，A 型核纤层蛋白扩散到活性染色质上，并在生肌基因附近的活性 H3K27ac 和 H3K4me3 组蛋白标记区域积累，这些基因的表达在没有 LAP2α 的情况下表达受损。染色质上 A 型核纤层蛋白的重组伴随着活性染色质标记 H3K27ac 的耗竭和生肌分化的显著受损。因此，LAP2α 和 A 型核纤层蛋白的相互作用对于核内核纤层蛋白 A/C 在染色质上的正确定位以实现有效的成肌分化至关重要。