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

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Binding Sites
  • Cell Differentiation
  • Erythroid Cells / cytology
  • Erythroid Cells / metabolism
  • Erythropoiesis / genetics
  • Feedback, Physiological*
  • Gene Expression Regulation, Developmental*
  • Humans
  • K562 Cells
  • Kruppel-Like Transcription Factors / genetics*
  • Kruppel-Like Transcription Factors / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Primary Cell Culture
  • Promoter Regions, Genetic
  • Protein Binding
  • Signal Transduction
  • Sp1 Transcription Factor / genetics*
  • Sp1 Transcription Factor / metabolism
  • Transcription, Genetic
  • beta-Globins / genetics*
  • beta-Globins / metabolism


  • KLF3 protein, human
  • Kruppel-Like Transcription Factors
  • MIRN23a microRNA, human
  • MIRN27 microRNA, human
  • MicroRNAs
  • Sp1 Transcription Factor
  • beta-Globins