Transcriptional and Epigenetic Mechanisms Regulating Normal and Aberrant Blood Cell Development
Transcriptional and Epigenetic Mechanisms Regulating Normal and Aberrant Blood Cell Development
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调节正常和异常血细胞发育的转录和表观遗传机制
DOI：
10.1007/978-3-642-45198-0_2
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Badenhorst P
中科院分区：
文献类型：
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作者：
Badenhorst P
果蝇(果蝇)拥有一种高效的天然免疫系统，可以防御包括细菌、真菌和寄生虫在内的病原体。病原体通过吞噬、包裹和黑化等机制被中和。被称为血细胞的循环细胞是先天免疫系统的关键组成部分，包括类似哺乳动物粒细胞-巨噬细胞谱系的细胞。调节果蝇造血祖细胞规范和分化的机制是高度保守的，这使得果蝇可以作为一个有用的模型来理解造血的转录调控。在这篇综述中，我将总结果蝇血细胞前体的中胚层起源，并描述与哺乳动物血管母细胞前体的相似之处。我将讨论调节三种主要血细胞类型分化的关键信号通路和转录因子。这与控制哺乳动物造血的转录电路有显著的相似之处，转录因子如GATA因子、RUNX家族成员和STAT蛋白影响果蝇血细胞的指定和分化。这些转录因子招募共抑制或共激活复合体，改变染色质结构来调节基因表达。我将讨论如何利用果蝇的造血室来探索依赖于ATP的染色质重塑复合体和组蛋白修饰复合体的功能。由于造血的关键调控因子是保守的，果蝇巨大的遗传适应性为分析RUNX1-ETO等致白血病融合蛋白的功能提供了一个强大的系统。在综述的最后部分，将讨论使用遗传筛选来确定新的RUNX1-ETO相互作用因子。
Drosophila(fruit flies) possess a highly effective innate immune system that provides defence against pathogens that include bacteria, fungi and parasites. Pathogens are neutralised by mechanisms that include phagocytosis, encapsulation and melanisation. Circulating cells called haemocytes are a key component of the innate immune system and include cells that resemble the granulocyte–macrophage lineages of mammals. The mechanisms that regulateDrosophilahaematopoietic progenitor specification and differentiation are highly conserved, allowingDrosophilato be used as a useful model to understand transcriptional regulation of haematopoiesis. In this review I will summarise the mesodermal origin ofDrosophilahaemocyte precursors and describe parallels with mammalian haemangioblast precursors. I will discuss key signalling pathways and transcription factors that regulate differentiation of the three principal haemocyte cell types. There are significant parallels with the transcriptional circuitry that controls mammalian haematopoiesis, with transcription factors such as GATA factors, RUNX family members and STAT proteins influencing the specification and differentiation ofDrosophilahaemocytes. These transcription factors recruit co-repressor or co-activator complexes that alter chromatin structure to regulate gene expression. I will discuss how theDrosophilahaematopoietic compartment has been used to explore function of ATP-dependent chromatin remodelling complexes and histone modifying complexes. As key regulators of haematopoiesis are conserved, the great genetic amenability ofDrosophilaoffers a powerful system to dissect function of leukaemogenic fusion proteins such as RUNX1-ETO. In the final section of the review the use of genetic screens to identify novel RUNX1-ETO interacting factors will be discussed.