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首页> 外文期刊>Current opinion in hematology >Integrative view on how erythropoietin signaling controls transcription patterns in erythroid cells
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Integrative view on how erythropoietin signaling controls transcription patterns in erythroid cells

机译：关于红细胞生成素信号传导控制红细胞细胞转录模式的整合视图

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Purpose of review Erythropoietin (EPO) is necessary and sufficient to trigger dynamic transcriptional patterns that drive the differentiation of erythroid precursor cells into mature, enucleated red cells. Because the molecular cloning and Food and Drug Administration approval for the therapeutic use of EPO over 30 years ago, a detailed understanding of how EPO works has advanced substantially. Yet, the precise epigenetic and transcriptional mechanisms by which EPO signaling controls erythroid expression patterns remains poorly understood. This review focuses on the current state of erythroid biology in regards to EPO signaling from human genetics and functional genomics perspectives. Recent findings The goal of this review is to provide an integrative view of the gene regulatory underpinnings for erythroid expression patterns that are dynamically shaped during erythroid differentiation. Here, we highlight vignettes connecting recent insights into a genome-wide association study linking an EPO mutation to anemia, a study linking EPO-signaling to signal transducer and activator of transcription 5 (STAT5) chromatin occupancy and enhancers, and studies that examine the molecular mechanisms driving topological chromatin organization in erythroid cells. Summary The genetic, epigenetic, and gene regulatory mechanisms underlying how hormone signal transduction influences erythroid gene expression remains only partly understood. A detailed understanding of these molecular pathways and how they intersect with one another will provide the basis for novel strategies to treat anemia and potentially other hematological diseases. As new regulators and signal transducers of EPO-signaling continue to emerge, new clinically relevant targets may be identified that improve the specificity and effectiveness of EPO therapy.
机译：回顾促红细胞生成素（EPO）的目的是必要的并且足以触发动态转录模式，使红细胞前体细胞分化为成熟，即核红细胞。由于30年前ePO治疗利用的分子克隆和食品和药物管理局批准，详细了解EPO工程如何大幅提升。然而，EPO信号传导对红细胞表达模式的精确表观遗传和转录机制仍然是较差的。本综述重点介绍了人类遗传和功能基因组学视角的EPO信号传导的红细胞生物学的当前状态。最近的发现本综述是提供一种在红细胞分化期间动态形状的红细胞表达模式的基因调节内衬的集成视图。在这里，我们突出了将最近有见解的小插曲，将EPO突变与贫血联系起来，将EPO信号传递到信号传感器和转录5（STAT5）染色质占用和增强剂的研究，以及检查分子的研究在红细胞细胞中驾驶拓扑染色质组织的机制。发明内容遗传，表观遗传和基因调节机制依赖于激素信号转导影响红细胞基因表达的影响仍然是部分理解的。详细了解这些分子途径以及它们与彼此相交的方式将为治疗贫血和潜在的其他血液疾病的新策略提供基础。随着EPO信令的新调节器和信号传感器继续出现，可以识别新的临床相关靶标，提高EPO治疗的特异性和有效性。

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