The transcriptional programme controlled by Runx1 during early embryonic blood development

• Published in: Developmental biology Vol. 366; no. 2; pp. 404 - 419
• Main Authors: Tanaka, Yosuke, Joshi, Anagha, Wilson, Nicola K., Kinston, Sarah, Nishikawa, Shinichi, Göttgens, Berthold
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.06.2012; Elsevier
• Subjects: Animals; blood cells; Blood Cells - cytology; Cell Differentiation - genetics; Cell Lineage - genetics; ChIP-Seq; Core Binding Factor Alpha 2 Subunit - genetics; data collection; Early blood development; gene expression; Gene Expression Regulation, Developmental; Gene expresssion; genes; Genome; Genomes and Developmental Control; Haematopoiesis; Hematopoietic System - embryology; Hematopoietic System - physiology; in vivo studies; mammals; Mice; Platelet Membrane Glycoprotein IIb - genetics; Runx1; transcription (genetics); transcription factors; Transcription, Genetic; Transcriptional control; transcriptomics; Gene expresssion; ChIP-Seq; Transcriptional control; Early blood development; Runx1; Haematopoiesis
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2012.03.024

Transcription factors have long been recognised as powerful regulators of mammalian development yet it is largely unknown how individual key regulators operate within wider regulatory networks. Here we have used a combination of global gene expression and chromatin-immunoprecipitation approaches during the early stages of haematopoietic development to define the transcriptional programme controlled by Runx1, an essential regulator of blood cell specification. Integrated analysis of these complementary genome-wide datasets allowed us to construct a global regulatory network model, which suggested that key regulators are activated sequentially during blood specification, but will ultimately collaborate to control many haematopoietically expressed genes. Using the CD41/integrin alpha 2b gene as a model, cellular and in vivo studies showed that CD41 is controlled by both Scl/Tal1 and Runx1 in fully specified blood cells, and initiation of CD41 expression in E7.5 embryos is severely compromised in the absence of Runx1. Taken together, this study represents the first global analysis of the transcriptional programme controlled by any key haematopoietic regulator during the process of early blood cell specification. Moreover, the concept of interplay between sequentially deployed core regulators is likely to represent a design principle widely applicable to the transcriptional control of mammalian development. ► Genome-scale analysis of Runx1 targets during early blood development. ► Integrated analysis of ES-cell and early mouse embryo expression profiles. ► Runx1 is a critical regulator of CD41 expression in early embryos. ► Connecting sequentially-activated regulators stabilises emerging networks.