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Developmentally regulated promoter-switch transcriptionally controls Runx1 function during embryonic hematopoiesis

机译:胚胎造血过程中发育调控的启动子开关转录控制Runx1功能。

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摘要

BackgroundAlternative promoters usage is an important paradigm in transcriptional control of mammalian gene expression. However, despite the growing interest in alternative promoters and their role in genome diversification, very little is known about how and on what occasions those promoters are differentially regulated. Runx1 transcription factor is a key regulator of early hematopoiesis and a frequent target of chromosomal translocations in acute leukemias. Mice deficient in Runx1 lack definitive hematopoiesis and die in mid-gestation. Expression of Runx1 is regulated by two functionally distinct promoters designated P1 and P2. Differential usage of these two promoters creates diversity in distribution and protein-coding potential of the mRNA transcripts. While the alternative usage of P1 and P2 likely plays an important role in Runx1 biology, very little is known about the function of the P1/P2 switch in mediating tissue and stage specific expression of Runx1 during development.
机译:背景技术替代启动子的使用是哺乳动物基因表达的转录控制中的重要范例。然而,尽管人们对替代启动子及其在基因组多样化中的作用越来越感兴趣,但是关于如何以及在什么情况下对这些启动子进行差异调节的了解却很少。 Runx1转录因子是早期造血的关键调节因子,也是急性白血病中染色体易位的常见靶标。缺乏Runx1的小鼠缺乏确定的造血功能,并在妊娠中期死亡。 Runx1的表达受两个功能不同的启动子P1和P2调控。这两个启动子的不同用法在mRNA转录物的分布和蛋白质编码潜力中产生了多样性。虽然P1和P2的替代用法可能在Runx1生物学中起重要作用,但对P1 / P2开关在发育过程中介导Runx1的组织和阶段特异性表达中的功能了解甚少。

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