Hmga2 is a direct target gene of RUNX1 and regulates expansion of myeloid progenitors in mice

Blood. 2014 Oct 2;124(14):2203-12. doi: 10.1182/blood-2014-02-554543. Epub 2014 Aug 22.


RUNX1 is a master transcription factor in hematopoiesis and mediates the specification and homeostasis of hematopoietic stem and progenitor cells (HSPCs). Disruptions in RUNX1 are well known to lead to hematologic disease. In this study, we sought to identify and characterize RUNX1 target genes in HSPCs by performing RUNX1 chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) using a murine HSPC line and complementing this data with our previously described gene expression profiling of primary wild-type and RUNX1-deficient HSPCs (Lineage(-)/cKit(+)/Sca1(+)). From this analysis, we identified and confirmed that Hmga2, a known oncogene, as a direct target of RUNX1. Hmga2 was strongly upregulated in RUNX1-deficient HSPCs, and the promoter of Hmga2 was responsive in a cell-type dependent manner upon coexpression of RUNX1. Conditional Runx1 knockout mice exhibit expansion of their HSPCs and myeloid progenitors as hallmark phenotypes. To further validate and establish that Hmga2 plays a role in inducing HSPC expansion, we generated mouse models of HMGA2 and RUNX1 deficiency. Although mice lacking both factors continued to display higher frequencies of HSPCs, the expansion of myeloid progenitors was effectively rescued. The data presented here establish Hmga2 as a transcriptional target of RUNX1 and a critical regulator of myeloid progenitor expansion.

Publication types

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

MeSH terms

  • Animals
  • Binding Sites
  • Cell Line
  • Core Binding Factor Alpha 2 Subunit / metabolism*
  • Gene Expression Regulation*
  • HMGA2 Protein / metabolism*
  • Hematopoiesis / physiology
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Jurkat Cells
  • K562 Cells
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Myeloid Progenitor Cells / cytology*
  • NIH 3T3 Cells
  • Phenotype
  • Transcription Factors / metabolism
  • Up-Regulation


  • Core Binding Factor Alpha 2 Subunit
  • HMGA2 Protein
  • Runx1 protein, mouse
  • Transcription Factors