Although the promyelocytic leukemia (PML) protein is renowned for regulating a wide range of cellular processes and as an essential component of PML nuclear bodies (PML-NBs), the mechanisms through which it exerts its broad physiological impact are far from fully elucidated. Here, we review recent studies supporting an emerging view that PML's pleiotropic effects derive, at least partially, from its role in regulating histone H3.3 chromatin assembly, a critical epigenetic mechanism. These studies suggest that PML maintains heterochromatin organization by restraining H3.3 incorporation. Examination of PML's contribution to H3.3 chromatin assembly in the context of the cell cycle and PML-NB assembly suggests that PML represses heterochromatic H3.3 deposition during S phase and that transcription and SUMOylation regulate PML's recruitment to heterochromatin. Elucidating PML’ s contributions to H3.3-mediated epigenetic regulation will provide insight into PML's expansive influence on cellular physiology and open new avenues for studying oncogenesis linked to PML malfunction.

中文翻译：

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PML 对 H3.3 染色质组装的调节：一种调节表观遗传的方法

尽管早幼粒细胞白血病 (PML) 蛋白以调节广泛的细胞过程和作为 PML 核体 (PML-NBs) 的重要组成部分而闻名，但它发挥其广泛生理影响的机制还远未完全阐明。在这里，我们回顾了最近支持一种新兴观点的研究，即 PML 的多效性至少部分源自其在调节组蛋白 H3.3 染色质组装中的作用，这是一种关键的表观遗传机制。这些研究表明 PML 通过抑制 H3.3 掺入来维持异染色质组织。在细胞周期和 PML-NB 组装的背景下检查 PML 对 H3.3 染色质组装的贡献表明 PML 在 S 期抑制异染色质 H3.3 沉积并且转录和 SUMOylation 调节 PML' s 招募异染色质。阐明 PML 对 H3.3 介导的表观遗传调控的贡献将有助于深入了解 PML 对细胞生理学的广泛影响，并为研究与 PML 故障相关的肿瘤发生开辟新途径。