A feedback loop consisting of microRNA-23a/27a and the β-like globin suppressors KLF3 and SP1 regulates globin gene expression.

Yanni Ma, Bin Wang, Fengbing Jiang, Dongsheng Wang, Huiwen Liu, Yunmeng Yan, He Dong, Fang Wang, Bei Gong, Yong zhu, Lei Dong, Haixin Yin, Zhongzu Zhang, Hualu Zhao, Zhikui Wu, Junwu Zhang, Jingguo Zhou*, Jia Yu*

Molecular and Cellular Biology. 2013 Aug 5. [Epub ahead of print] PMID: 23918807

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 miR-23a and 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 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 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 miR-23a∼27a∼24-2 cluster during erythropoiesis.