Format

Send to:

Choose Destination
See comment in PubMed Commons below
Dev Biol. 2012 Jun 15;366(2):404-19. doi: 10.1016/j.ydbio.2012.03.024. Epub 2012 Apr 21.

The transcriptional programme controlled by Runx1 during early embryonic blood development.

Author information

  • 1Laboratory for Stem Cell Biology, RIKEN Center for Developmental Biology, Kobe, Japan.

Abstract

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.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID:
22554697
[PubMed - indexed for MEDLINE]
PMCID:
PMC3430866
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk