Benoit Jane, Sheikhbahaei Mahdi Khadem, Dennis Jonathan
Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
J Cancer Biol. 2021;2(2):51-55. doi: 10.46439/cancerbiology.2.024.
The nucleosome, consisting of ~150bp of DNA wrapped around a core histone octamer, is a regulator of nuclear events that contributes to gene expression and cell fate. Nucleosome organization at promoters and their associated remodeling events are important regulators of access to the genome. Occupancy alone, however, is not the only nucleosomal characteristic that plays a role in genome regulation. Nucleosomes at the transcription start sites (TSSs) of genes show differential sensitivity to micrococcal nuclease (MNase) and this differential sensitivity is linked to transcription and regulatory factor binding events. Recently, lymphoblastoid cells treated with heat-killed were shown to exhibit increased MNase sensitivity specifically at genes implicated in immune responses. Increased sensitivity at the -1-nucleosome permitted transcription factor and RNA Pol II binding events. This system illustrates how cytoplasmic signals induce altered chromatin states to produce a specific cellular response to a stimulus. Innate immune activation is a longstanding model for inducible promoters, transcriptional activation, and differential nucleosomal sensitivity in response to immune activation and offers a model that may be largely applicable to other specific cellular responses including viral infection and cancer. Previous work has shown that early transformation events are associated with prolonged nucleosome occupancy changes that are not observed later in cancer progression. Herein, we propose a model in which we suggest that detailed studies of nucleosomal occupancy and sensitivity in response to specific stimuli will provide insight into the regulation of nuclear events in cancer and other biological processes.
核小体由缠绕在核心组蛋白八聚体周围的约150个碱基对的DNA组成，是核事件的调节因子，有助于基因表达和细胞命运。启动子处的核小体组织及其相关的重塑事件是基因组可及性的重要调节因子。然而，仅仅占据并不是在基因组调节中起作用的唯一核小体特征。基因转录起始位点（TSS）处的核小体对微球菌核酸酶（MNase）表现出不同的敏感性，这种不同的敏感性与转录和调节因子结合事件有关。最近，用热灭活处理的淋巴母细胞被证明在与免疫反应相关的基因处特异性地表现出MNase敏感性增加。-1-核小体处敏感性的增加允许转录因子和RNA聚合酶II结合事件发生。该系统说明了细胞质信号如何诱导染色质状态改变，以产生对刺激的特定细胞反应。先天免疫激活是诱导型启动子、转录激活和对免疫激活的不同核小体敏感性的长期模型，并提供了一个可能在很大程度上适用于其他特定细胞反应（包括病毒感染和癌症）的模型。先前的研究表明，早期转化事件与长期的核小体占据变化有关，而在癌症进展后期未观察到这种变化。在此，我们提出一个模型，我们认为对核小体占据和对特定刺激的敏感性进行详细研究将有助于深入了解癌症和其他生物学过程中核事件的调节。
