Faculty of Life Sciences & Medicine, School of Basic and Medical Biosciences, Centre of Human and Applied Physiological Sciences, King's College London, London, UK.
J Muscle Res Cell Motil. 2019 Dec;40(3-4):335-341. doi: 10.1007/s10974-019-09549-3.
Skeletal muscle fibres are large, elongated multinucleated cells. Each nucleus within a myofibre is responsible for generating gene products for a finite volume of cytoplasm-the myonuclear domain (MND). Variation in MND sizes during atrophy, hypertrophy and disease states, are common. The factors that contribute to definitive MND sizes are not yet fully understood. Previous work has shown that peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1-α) modulates MND volume, presumably to support increased biogenesis of mitochondria. The transcriptional co-regulator peroxisome proliferator-activated receptor gamma coactivator 1β (PGC1-β) is a homologue of PGC1-α with overlapping functions. To investigate the role of this protein in MND size regulation, we studied a mouse skeletal muscle specific knockout (cKO). Myofibres were isolated from the fast twitch extensor digitorum longus (EDL) muscle, membrane-permeabilised and analysed in 3 dimensions using confocal microscopy. PGC1-β ablation resulted in no significant difference in MND size between cKO and wild type (WT) mice, however, subtle differences in nuclear morphology were observed. To determine whether these nuclear shape changes were associated with alterations in global transcriptional activity, acetyl histone H3 immunostaining was carried out. We found there was no significant difference in nuclear fluorescence intensity between the two genotypes. Overall, the results suggest that PGC-1α and PGC-1β play different roles in regulating nuclear organisation in skeletal muscle; however, further work is required to pinpoint their exact functions.
骨骼肌纤维是大型的、长形的多核细胞。肌纤维内的每个核负责为有限体积的细胞质——肌核域（MND）生成基因产物。在萎缩、肥大和疾病状态下，MND 大小的变化很常见。导致确定的 MND 大小的因素尚未完全理解。以前的工作表明，过氧化物酶体增殖物激活受体γ共激活因子 1α（PGC1-α）调节 MND 体积，大概是为了支持线粒体生物发生的增加。转录共激活因子过氧化物酶体增殖物激活受体γ共激活因子 1β（PGC1-β）是 PGC1-α 的同源物，具有重叠的功能。为了研究该蛋白在 MND 大小调节中的作用，我们研究了一种骨骼肌特异性敲除（cKO）的小鼠。从快速抽搐伸肌 digitorum longus（EDL）肌肉中分离肌纤维，透膜后使用共聚焦显微镜在 3 维空间进行分析。PGC1-β 缺失在 cKO 和野生型（WT）小鼠之间的 MND 大小没有显著差异，然而，观察到核形态的细微差异。为了确定这些核形状变化是否与整体转录活性的改变有关，进行了乙酰化组蛋白 H3 免疫染色。我们发现两种基因型之间的核荧光强度没有显著差异。总体而言，结果表明 PGC-1α 和 PGC-1β 在调节骨骼肌核组织方面发挥不同的作用；然而，需要进一步的工作来确定它们的确切功能。
