PUBLICATION

Meis1, Hi1α, and GATA1 are integrated into a hierarchical regulatory network to mediate primitive erythropoiesis

Authors
Chung, H.Y., Lin, B.A., Lin, Y.X., Chang, C.W., Tzou, W.S., Pei, T.W., Hu, C.H.
ID
ZDB-PUB-210909-13
Date
2021
Source
FASEB journal : official publication of the Federation of American Societies for Experimental Biology   35: e21915 (Journal)
Registered Authors
Hu, Chin-Hwa
Keywords
Gata1, Meis1, hypoxia inducible factor 1 alpha, primitive erythropoiesis, regulatory network, zebrafish
MeSH Terms
  • Animals
  • Chromatin Immunoprecipitation
  • Erythrocytes/cytology
  • Erythrocytes/metabolism
  • Erythroid Cells/cytology
  • Erythroid Cells/metabolism*
  • Erythropoiesis*/genetics
  • GATA1 Transcription Factor/genetics
  • GATA1 Transcription Factor/metabolism*
  • Gene Expression Regulation, Developmental
  • Hypoxia-Inducible Factor 1, alpha Subunit/deficiency
  • Hypoxia-Inducible Factor 1, alpha Subunit/genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*
  • Myeloid Ecotropic Viral Integration Site 1 Protein/deficiency
  • Myeloid Ecotropic Viral Integration Site 1 Protein/genetics
  • Myeloid Ecotropic Viral Integration Site 1 Protein/metabolism*
  • Pre-B-Cell Leukemia Transcription Factor 1/deficiency
  • Pre-B-Cell Leukemia Transcription Factor 1/genetics
  • Transcription, Genetic
  • Zebrafish/blood
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
34496088 Full text @ FASEB J.
Abstract
During development, erythroid cells are generated by two waves of hematopoiesis. In zebrafish, primitive erythropoiesis takes place in the intermediate cell mass region, and definitive erythropoiesis arises from the aorta-gonad mesonephros. TALE-homeoproteins Meis1 and Pbx1 function upstream of GATA1 to specify the erythroid lineage. Embryos lacking Meis1 or Pbx1 have weak gata1 expression and fail to produce primitive erythrocytes. Nevertheless, the underlying mechanism of how Meis1 and Pbx1 mediate gata1 transcription in erythrocytes remains unclear. Here we show that Hif1α acts downstream of Meis1 to mediate gata1 expression in zebrafish embryos. Inhibition of Meis1 expression resulted in suppression of hif1a expression and abrogated primitive erythropoiesis, while injection with in vitro-synthesized hif1α mRNA rescued gata1 transcription in Meis1 morphants and recovered their erythropoiesis. Ablation of Hif1α expression either by morpholino knockdown or Crispr-Cas9 knockout suppressed gata1 transcription and abrogated primitive erythropoiesis. Results of chromatin immunoprecipitation assays showed that Hif1α associates with hypoxia-response elements located in the 3'-flanking region of gata1 during development, suggesting that Hif1α regulates gata1 expression in vivo. Together, our results indicate that Meis1, Hif1α, and GATA1 indeed comprise a hierarchical regulatory network in which Hif1α acts downstream of Meis1 to activate gata1 transcription through direct interactions with its cis-acting elements in primitive erythrocytes.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping