title: RUNX1 positively regulates a cell adhesion and migration program in murine hemogenic endothelium prior to blood emergence.
abstract: During ontogeny, the transcription factor RUNX1 governs the emergence of definitive hematopoietic cells from specialized endothelial cells called hemogenic endothelium (HE). The ultimate consequence of this endothelial-to-hematopoietic transition is the concomitant activation of the hematopoietic program and downregulation of the endothelial program. However, due to the rare and transient nature of the HE, little is known about the initial role of RUNX1 within this population. We, therefore, developed and implemented a highly sensitive DNA adenine methyltransferase identification-based methodology, including a novel data analysis pipeline, to map early RUNX1 transcriptional targets in HE cells. This novel transcription factor binding site identification protocol should be widely applicable to other low abundance cell types and factors. Integration of the RUNX1 binding profile with gene expression data revealed an unexpected early role for RUNX1 as a positive regulator of cell adhesion- and migration-associated genes within the HE. This suggests that RUNX1 orchestrates HE cell positioning and integration prior to the release of hematopoietic cells. Overall, our genome-wide analysis of the RUNX1 binding and transcriptional profile in the HE provides a novel comprehensive resource of target genes that will facilitate the precise dissection of the role of RUNX1 in early blood development.
authors.affiliation: Cancer Research UK Stem Cell Biology Group, and.
authors.forename: Michael
authors.initials: M
authors.lastname: Lie-A-Ling
authors.affiliation: Cancer Research UK Stem Cell Biology Group, and Cancer Research UK Computational Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, United Kingdom;
authors.forename: Elli
authors.initials: E
authors.lastname: Marinopoulou
authors.affiliation: Cancer Research UK Computational Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, United Kingdom;
authors.forename: Yaoyong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Cancer Research UK Stem Cell Biology Group, and.
authors.forename: Rahima
authors.initials: R
authors.lastname: Patel
authors.affiliation: Faculty of Biochemistry, Biophysics and Biotechnology Department, Jagiellonian University, Kraków, Poland;
authors.forename: Monika
authors.initials: M
authors.lastname: Stefanska
authors.affiliation: Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom; and.
authors.forename: Constanze
authors.initials: C
authors.lastname: Bonifer
authors.affiliation: Cancer Research UK Computational Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, United Kingdom;
authors.forename: Crispin
authors.initials: C
authors.lastname: Miller
authors.affiliation: Cancer Research UK Stem Cell Haematopoiesis Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, United Kingdom.
authors.forename: Valerie
authors.initials: V
authors.lastname: Kouskoff
authors.affiliation: Cancer Research UK Stem Cell Biology Group, and.
authors.forename: Georges
authors.identifier: http://orcid.org/0000-0002-5630-2417
authors.initials: G
authors.lastname: Lacaud
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006410:Hematopoiesis / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C493726:Runx1 protein, mouse