PUBLICATION

Overlapping Requirements for Tet2 and Tet3 in Normal Development and Hematopoietic Stem Cell Emergence

Authors
Li, C., Lan, Y., Schwartz-Orbach, L., Korol, E., Tahiliani, M., Evans, T., Goll, M.G.
ID
ZDB-PUB-150811-3
Date
2015
Source
Cell Reports   12(7): 1133-43 (Journal)
Registered Authors
Evans, Todd, Goll, Mary
Keywords
none
MeSH Terms
  • Animals
  • Dioxygenases/genetics
  • Dioxygenases/metabolism*
  • Embryonic Development
  • Endothelial Progenitor Cells/cytology
  • Endothelial Progenitor Cells/metabolism
  • Gene Expression Regulation, Developmental
  • Hematopoiesis*
  • Hematopoietic Stem Cells/cytology
  • Hematopoietic Stem Cells/metabolism*
  • Receptors, Notch/metabolism
  • Signal Transduction
  • Transcription Factors/metabolism
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
26257178 Full text @ Cell Rep.
Abstract
The Tet family of methylcytosine dioxygenases (Tet1, Tet2, and Tet3) convert 5-methylcytosine to 5-hydroxymethylcytosine. To date, functional overlap among Tet family members has not been examined systematically in the context of embryonic development. To clarify the potential for overlap among Tet enzymes during development, we mutated the zebrafish orthologs of Tet1, Tet2, and Tet3 and examined single-, double-, and triple-mutant genotypes. Here, we identify Tet2 and Tet3 as the major 5-methylcytosine dioxygenases in the zebrafish embryo and uncover a combined requirement for Tet2 and Tet3 in hematopoietic stem cell (HSC) emergence. We demonstrate that Notch signaling in the hemogenic endothelium is regulated by Tet2/3 prior to HSC emergence and show that restoring expression of the downstream gata2b/scl/runx1 transcriptional network can rescue HSCs in tet2/3 double mutant larvae. Our results reveal essential, overlapping functions for tet genes during embryonic development and uncover a requirement for 5hmC in regulating HSC production.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping