Department of Biochemistry, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China.
Mol Cell Biol. 2013 Oct;33(20):3994-4007. doi: 10.1128/MCB.00623-13. Epub 2013 Aug 5.
The developmental stage-specific expression of the human β-like globin genes has been studied for decades, and many transcriptional factors as well as other important cis elements have been identified. However, little is known about the microRNAs that potentially regulate β-like globin gene expression directly or indirectly during erythropoiesis. In this study, we show that microRNA 23a (miR-23a) and miR-27a promote β-like globin gene expression in K562 cells and primary erythroid cells through targeting of the transcription factors KLF3 and SP1. Intriguingly, miR-23a and miR-27a further enhance the transcription of β-like globin genes through repression of KLF3 and SP1 binding to the β-like globin gene locus during erythroid differentiation. Moreover, KLF3 can bind to the promoter of the miR-23a∼27a∼24-2 cluster and suppress this microRNA cluster expression. Hence, a positive feedback loop comprised of KLF3 and miR-23a promotes the expression of β-like globin genes and the miR-23a∼27a∼24-2 cluster during erythropoiesis.
人类β样球蛋白基因的发育阶段特异性表达已研究了数十年，已经鉴定出许多转录因子以及其他重要的顺式元件。然而，对于在红细胞生成过程中可能直接或间接调节β样球蛋白基因表达的 microRNA 知之甚少。在这项研究中，我们表明 microRNA 23a（miR-23a）和 miR-27a 通过靶向转录因子 KLF3 和 SP1 促进 K562 细胞和原代红细胞中β样球蛋白基因的表达。有趣的是，miR-23a 和 miR-27a 通过抑制 KLF3 和 SP1 与β样球蛋白基因座结合，在红细胞分化过程中进一步增强β样球蛋白基因的转录。此外，KLF3 可以结合到 miR-23a∼27a∼24-2 簇的启动子上并抑制该 microRNA 簇的表达。因此，由 KLF3 和 miR-23a 组成的正反馈回路在红细胞生成过程中促进β样球蛋白基因和 miR-23a∼27a∼24-2 簇的表达。
