中国环境科学研究院环境基准与风险评估国家重点实验室,北京 100012
国家自然科学基金(42177259)资助项目。
State Key Laboratory of Environmental Criteria and Risk Assessment,Chinese Research Academy of Environmental Sciences, Beijing 100012, China
This work was supported by a grant from The National Natural Science Foundation of China (42177259).
叉头框蛋白A(FoxA)基因家族作为一个保守的转录因子家族,在调控胚胎发育、细胞分化以及疾病发生过程中起着关键作用。FoxA最初被命名为Hnf3α(肝细胞核因子3α),在肝脏特异性基因的激活和形态发生过程中具有重要功能。研究表明,FoxA蛋白能够与特定的DNA序列以及缠绕在核小体上的DNA相互作用,通过改变染色质局部结构来调控基因表达,因此被称为“先锋因子”(pioneer factors)。FoxA家族有3个成员:FoxA1、FoxA2和FoxA3。FoxA1主要在肺、肝脏、胰腺和前列腺等内胚层来源的器官中表达,参与调控激素代谢、细胞周期和细胞增殖。FoxA2主要在脊椎动物的脊髓底板中表达,调控神经管背腹模式的建立。FoxA3主要在睾丸中表达,调控生殖细胞的形成。在基因家族现存的变体中,foxa2-/-基因突变斑马鱼胚胎能够存活,为解释胚胎发育提供可能。现有研究表明,FoxA参与早期胚胎发育过程、癌症以及代谢相关疾病的发生。本文在总结FoxA基因发现、蛋白质表达和生物学功能的基础上,提出需要解决的科学问题,为读者更好地理解FoxA基因在胚胎发育和癌症发生中的作用提供依据。
The FoxA genes belong to a conserved family of transcription factors, that play a crucial role in regulating embryonic development, cellular differentiation, and disease pathogenesis. Initially identified as hepatocyte nuclear factor 3α (Hnf3α), FoxA is pivotal in activating liver-specific genes and contributing to liver morphogenesis. Studies have shown that FoxA proteins interact with specific DNA sequences and nucleosome-bound DNA, altering the local chromatin structure to regulate gene expression. The unique ability has earned them the designation of “pioneer factors”. The FoxA family comprises three members: FoxA1, FoxA2, and FoxA3. FoxA1 is predominantly expressed in endoderm-derived organs such as the lungs, liver, pancreas, and prostate, where it regulates hormone metabolism, cell cycle, and cell proliferation. FoxA2 is primarily expressed in the floor plate of the vertebrate spinal cord, where it plays a key role in establishing the dorsal-ventral patterning of the neural tube. FoxA3 is mainly expressed in the testes, where it regulates germ cell formation. FoxA genes exhibit functional diversity in embryonic development across different species, offering insights into their evolutionary roles. For instance, zebrafish embryos with mutations in the foxa2-/- gene can survive, providing an opportunity to study embryonic development mechanisms. Currently, a growing body of research suggests that FoxA genes are involved in early embryonic development, cancer, and metabolism-related diseases. This paper summarizes the discovery, expression patterns, and biological functions of the FoxA genes while identifying key scientific questions that remain unresolved. It aims to provide readers a solid scientific basis for understanding the molecular mechanisms through which FoxA genes regulate embryonic development and contribute to cancer pathogenesis.
王静涵,杨立新.叉头框蛋白A基因在进化、发育和疾病中的功能[J].生物化学与生物物理进展,2025,52(4):869-881
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