RUNX1 positively regulates a cell adhesion and migration program in murine hemogenic endothelium prior to blood emergence

Michael Lie-A-Ling, Elli Marinopoulou, Yaoyong Li, Rahima Patel, Monika Stefanska, Constanze Bonifer, Crispin Miller, Valerie Kouskoff, Georges Lacaud

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

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 down-regulation 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 DamID (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.

Original languageEnglish
Pages (from-to)e11-e20
JournalBlood
Volume124
Issue number11
Early online date31 Jul 2014
DOIs
Publication statusPublished - 11 Sep 2014

Bibliographical note

Copyright © 2014 American Society of Hematology.

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