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 Blood, 21 May 2009, Vol. 113, No. 21, pp. 5121-5124.
Prepublished online as a Blood First Edition Paper on March 25, 2009; DOI 10.1182/blood-2008-12-193003.

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HEMATOPOIESIS AND STEM CELLS

Brief report

The mouse Runx1 +23 hematopoietic stem cell enhancer confers hematopoietic specificity to both Runx1 promoters

Thomas Bee1, Emma L.K. Ashley1, Sorrel R.B. Bickley1, Andrew Jarratt1, Pik-Shan Li1, Jackie Sloane-Stanley1, Berthold Göttgens2, and Marella F.T.R. de Bruijn1

1 Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford University, Oxford; and 2 Cambridge University Department of Haematology, Cambridge Institute for Medical Research, Cambridge, United Kingdom

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 2 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 spatiotemporal 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 colonization, in a +23-specific pattern.


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