A novel complex, RUNX1-MYEF2, represses hematopoietic genes in erythroid cells

Research output: Contribution to journalArticle

Authors

  • Boet van Riel
  • Tibor Pakozdi
  • Rutger Brouwer
  • Kapil Tuladhar
  • Vedran Franke
  • Jan Christian Bryne
  • Ruud Jorna
  • Erik Jan Rijkers
  • Wilfred van Ijcken
  • Charlotte Andrieu-Soler
  • Jeroen Demmers
  • Roger Patient
  • Eric Soler
  • Boris Lenhard
  • Frank Grosveld

Colleges, School and Institutes

External organisations

  • Erasmus University Medical Center
  • University of Bergen
  • Weatherall Institute of Molecular Medicine
  • Cancer Genomics Center
  • Imperial College London, and MRC Clinical Sciences Centre
  • Center for Biomedical Genetics

Abstract

RUNX1 is known to be an essential transcription factor for generating hematopoietic stem cells (HSC), but much less is known about its role in the downstream process of hematopoietic differentiation. RUNX1 has been shown to be part of a large transcription factor complex, together with LDB1, GATA1, TAL1, and ETO2 (N. Meier et al., Development 133:4913- 4923, 2006) in erythroid cells. We used a tagging strategy to show that RUNX1 interacts with two novel protein partners, LSD1 and MYEF2, in erythroid cells. MYEF2 is bound in undifferentiated cells and is lost upon differentiation, whereas LSD1 is bound in differentiated cells. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) and microarray expression analysis were used to show that RUNX1 binds approximately 9,000 target sites in erythroid cells and is primarily active in the undifferentiated state. Functional analysis shows that a subset of the target genes is suppressed by RUNX1 via the newly identified partner MYEF2. Knockdown of Myef2 expression in developing zebrafish results in a reduced number of HSC.

Details

Original languageEnglish
Pages (from-to)3814-3822
Number of pages9
JournalMolecular and Cellular Biology
Volume32
Issue number19
Publication statusPublished - 1 Oct 2012

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