PUBLICATION

A Novel Complex, RUNX1-MYEF2, Represses Hematopoietic Genes in Erythroid Cells

Authors
van Riel, B., Pakozdi, T., Brouwer, R., Monteiro, R., Tuladhar, K., Franke, V., Bryne, J.C., Jorna, R., Rijkers, E.J., van Ijcken, W., Andrieu-Soler, C., Demmers, J., Patient, R., Soler, E., Lenhard, B., and Grosveld, F.
ID
ZDB-PUB-120718-42
Date
2012
Source
Molecular and cellular biology   32(19): 3814-3822 (Journal)
Registered Authors
Patient, Roger K.
Keywords
none
MeSH Terms
  • Animals
  • Cell Line, Tumor
  • Core Binding Factor Alpha 2 Subunit/genetics
  • Core Binding Factor Alpha 2 Subunit/metabolism*
  • DNA/metabolism
  • Erythroid Cells/metabolism*
  • Gene Expression Regulation, Developmental*
  • Gene Knockdown Techniques
  • Hematopoiesis*
  • Histone Demethylases
  • Mice
  • Morpholinos/administration & dosage
  • Morpholinos/genetics
  • Multiprotein Complexes/metabolism*
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism*
  • Oxidoreductases, N-Demethylating/metabolism*
  • Protein Binding
  • Repressor Proteins/genetics
  • Repressor Proteins/metabolism*
  • Zebrafish/embryology
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
22801375 Full text @ Mol. Cell. Biol.
Abstract

RUNX1 is known to be an essential transcription factor to generate 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 (25) in erythroid cells. Here a tagging strategy was used 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, while LSD1 is bound in differentiated cells. ChIP-seq analysis and microarray expression analysis were used to show that RUNX1 binds approximately nine thousand 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. Knock down of Myef2 expression in developing zebrafish results in a reduced number of HSC.

Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Errata and Notes