title: The mouse Runx1 +23 hematopoietic stem cell enhancer confers hematopoietic specificity to both Runx1 promoters.
abstract: 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.
authors.affiliation: Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford University, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bee
authors.forename: Emma L K
authors.initials: EL
authors.lastname: Ashley
authors.forename: Sorrel R B
authors.initials: SR
authors.lastname: Bickley
authors.forename: Andrew
authors.initials: A
authors.lastname: Jarratt
authors.forename: Pik-Shan
authors.initials: PS
authors.lastname: Li
authors.forename: Jackie
authors.initials: J
authors.lastname: Sloane-Stanley
authors.forename: Berthold
authors.initials: B
authors.lastname: Göttgens
authors.forename: Marella F T R
authors.initials: MF
authors.lastname: de Bruijn