PUBLICATION

Sumoylation of CCAAT/enhancer-binding protein α promotes the biased primitive hematopoiesis of zebrafish

Authors
Yuan, H., Zhou, J., Deng, M., Zhang, Y., Chen, Y., Jin, Y., Zhu, J., Chen, S.J., The, H.D., Chen, Z., Liu, T.X., and Zhu, J.
ID
ZDB-PUB-110602-27
Date
2011
Source
Blood   117(26): 7014-7020 (Journal)
Registered Authors
Chen, Yi, Chen, Zhu, Deng, Min, Jin, Yi, Liu, Ting Xi, Zhang, Yong
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • CCAAT-Enhancer-Binding Protein-alpha/genetics
  • CCAAT-Enhancer-Binding Protein-alpha/physiology*
  • Cell Line
  • Cell Lineage
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/metabolism*
  • GATA1 Transcription Factor/genetics
  • GATA1 Transcription Factor/metabolism
  • Gene Silencing
  • Genes, Reporter
  • Hematopoiesis, Extramedullary*
  • Humans
  • Mesoderm
  • Myeloid Progenitor Cells
  • Myelopoiesis
  • Peroxidase/genetics
  • Peroxidase/metabolism
  • Protein Isoforms/antagonists & inhibitors
  • Protein Isoforms/genetics
  • Protein Isoforms/physiology
  • Recombinant Fusion Proteins
  • Small Ubiquitin-Related Modifier Proteins/antagonists & inhibitors
  • Small Ubiquitin-Related Modifier Proteins/genetics
  • Small Ubiquitin-Related Modifier Proteins/metabolism*
  • Sumoylation*
  • Up-Regulation*
  • Zebrafish
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Zebrafish Proteins/physiology*
PubMed
21596856 Full text @ Blood
Abstract
Hematopoiesis is evolutionarily conserved from zebrafish to mammals, including both primitive and definitive waves during embryogenesis. Primitive hematopoiesis is dominated by erythropoiesis with limited myelopoiesis. Protein sumoylation, a ubiquitination-like post-translational protein modification, is implicated in a variety of biochemical processes, notably transcriptional repression. We show that loss of SUMO paralogs triggers a sharp up-regulation of the myeloid-specific marker mpo and down-regulation of the erythroid-specific marker gata1 in myelo-erythroid progenitor cells (MPCs) in the intermediate cell mass (ICM) during primitive hematopoiesis. Accordingly, in transgenic zebrafish lines, hyposumoylation expands myelopoiesis at the expense of erythropoiesis. A SUMO-C/ebpα fusion restores the normal myelopoiesis/erythropoiesis balance, suggesting that sumoylation status of C/ebpα contributes to myelo-erythroid lineage determination. Our results thus implicate sumoylation in early lineage determination and point out the possible molecular mechanism underlying the puzzling biased primitive hematopoiesis in vertebrates.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping