Submitted December 18, 2008
Accepted March 8, 2009
The mouse Runx1 +23 hematopoietic stem cell enhancer confers hematopoietic specificity to both Runx1 promoters
Thomas Bee, Emma L.K. Ashley, Sorrel R.B. Bickley, Andrew Jarratt, Pik-Shan Li, Jackie Sloane-Stanley, Berthold Gottgens, and Marella F.T.R. de Bruijn*
MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford University, Oxford, United Kingdom
Cambridge University Department of Haematology, Cambridge Institute for Medical Research, Cambridge, United Kingdom
* Corresponding author; email: marella.debruijn{at}imm.ox.ac.uk.
The transcription factor Runx1 plays a pivotal role in hematopoietic stem cell (HSC) emergence and studies into its transcriptional regulation should give insight into the critical steps of HSC specification. Recently, we identified the Runx1 +23 enhancer that targets reporter gene expression to the first emerging HSCs of the mouse embryo when linked to the heterologous hsp68 promoter. Endogenous Runx1 is transcribed from two alternative promoters, P1 and P2. Here, we examined the in vivo cis-regulatory potential of these alternative promoters and asked whether they act with and contribute to the spatio-temporal specific expression of the Runx1 +23 enhancer. Our results firmly establish that, in contrast to zebrafish runx1, mouse Runx1 promoter sequences do not confer any hematopoietic specificity in transgenic embryos. Yet, both mouse promoters act with the +23 enhancer to drive reporter gene expression to sites of HSC emergence and colonisation, in a +23 specific pattern.
