Hypoxia-inducible factor (HIF), a central regulator for detecting and adapting to cellular oxygen levels, transcriptionally activates genes modulating oxygen homeostasis and metabolic activation. Beyond this, HIF influences many other processes. Hypoxia, in part through HIF-dependent mechanisms, influences epigenetic factors, including DNA methylation and histone acetylation, which modulate hypoxia-responsive gene expression in cells. Hypoxia profoundly affects expression of many noncoding RNAs classes that have clinicopathological implications in cancer. HIF can regulate noncoding RNAs production, while, conversely, noncoding RNAs can modulate HIF expression. There is recent evidence for crosstalk between circadian rhythms and hypoxia-induced signaling, suggesting involvement of molecular clocks in adaptation to fluxes in nutrient and oxygen sensing. HIF induces increased production of cellular vesicles facilitating intercellular communication at a distance-for example, promoting angiogenesis in hypoxic tumors. Understanding the complex networks underlying cellular and genomic regulation in response to hypoxia via HIF may identify novel and specific therapeutic targets.

中文翻译：

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缺氧诱导因子生物学进展。

缺氧诱导因子 (HIF) 是一种用于检测和适应细胞氧水平的中央调节因子，它通过转录激活调节氧稳态和代谢激活的基因。除此之外，HIF 还会影响许多其他过程。缺氧部分通过 HIF 依赖性机制影响表观遗传因素，包括 DNA 甲基化和组蛋白乙酰化，它们调节细胞中缺氧反应基因的表达。缺氧会深刻影响许多在癌症中具有临床病理学意义的非编码 RNA 类的表达。HIF 可以调节非编码 RNA 的产生，而相反，非编码 RNA 可以调节 HIF 的表达。最近有证据表明昼夜节律和缺氧诱导的信号之间存在串扰，表明分子钟参与适应营养和氧气传感中的通量。HIF 诱导细胞囊泡的产生增加，从而促进远距离的细胞间通讯——例如，促进缺氧肿瘤中的血管生成。了解通过 HIF 响应缺氧的细胞和基因组调控的复杂网络可以确定新的和特定的治疗靶点。