Lamin A/C sustains PcG protein architecture, maintaining transcriptional repression at target genes.
Lamin A/C sustains PcG protein architecture, maintaining transcriptional repression at target genes.
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DOI：
10.1083/jcb.201504035
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发表时间：
2015-11-09
期刊：
影响因子：
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通讯作者：
Lanzuolo C
中科院分区：
文献类型：
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作者：
Cesarini E;Mozzetta C;Marullo F;Gregoretti F;Gargiulo A;Columbaro M;Cortesi A;Antonelli L;Di Pelino S;Squarzoni S;Palacios D;Zippo A;Bodega B;Oliva G;Lanzuolo C
核纤层蛋白A/C，这是进化所需的调制Polycomb组（PcG）蛋白依赖性转录抑制通过维持PcG蛋白核结构的减少，导致PcG蛋白扩散和肌肉分化。除了为核膜提供结构外，核纤层蛋白A/C还参与转录调控。然而，它与表观遗传因素的相互作用以及这种相互作用如何影响生理过程仍然未被探索。发育和分化的关键表观遗传调节因子是蛋白质的Polycomb组（PcG），在细胞核中组织为显微镜可见的病灶。在这里，我们表明，核纤层蛋白A/C是进化所需的正确的PcG蛋白核区室化。新的图像分析算法支持的共聚焦显微镜显示，核纤层蛋白A/C敲低导致PcG蛋白焦点拆卸和PcG蛋白分散。这会导致从染色质上脱落和PcG蛋白介导的高级结构缺陷，从而导致PcG蛋白抑制功能受损。以肌源性分化为模型，我们发现，由于PcG蛋白介导的转录抑制的改变，在分化开始时核纤层蛋白A/C的水平降低导致了对肌源性程序的预期。总的来说，我们的研究结果表明，核纤层蛋白A/C可以通过调节PcG蛋白表观遗传因子来调节转录。
Reduction of lamin A/C, which is evolutionarily required for the modulation of Polycomb group (PcG) protein–dependent transcriptional repression by sustaining PcG protein nuclear architecture, leads to PcG protein diffusion and to muscle differentiation. Beyond its role in providing structure to the nuclear envelope, lamin A/C is involved in transcriptional regulation. However, its cross talk with epigenetic factors—and how this cross talk influences physiological processes—is still unexplored. Key epigenetic regulators of development and differentiation are the Polycomb group (PcG) of proteins, organized in the nucleus as microscopically visible foci. Here, we show that lamin A/C is evolutionarily required for correct PcG protein nuclear compartmentalization. Confocal microscopy supported by new algorithms for image analysis reveals that lamin A/C knock-down leads to PcG protein foci disassembly and PcG protein dispersion. This causes detachment from chromatin and defects in PcG protein–mediated higher-order structures, thereby leading to impaired PcG protein repressive functions. Using myogenic differentiation as a model, we found that reduced levels of lamin A/C at the onset of differentiation led to an anticipation of the myogenic program because of an alteration of PcG protein–mediated transcriptional repression. Collectively, our results indicate that lamin A/C can modulate transcription through the regulation of PcG protein epigenetic factors.