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A role for the transcription intermediary factor 2 in zebrafish myelopoiesis
Julia Zhuravleva1, Eric Solary, Johanna Chluba
1Inserm, University of Burgundy, Dijon, France.
Objective:
TIF2 is fused with MOZ in the inv(8)(p11q13) acute myeloid leukemia. TIF2, member of the p160 family, is a histone acetyl transferase (HAT). Deletion of p160 genes were performed in mice. Some observations suggest that p160 family members may perform overlapping functions in mice. Therefore, we decided to choose the zebrafish model to study TIF2. The aim of this study was to characterize the role of this HAT during embryonic development.
Material And Methods:
We use antisense, morpholino-modified oligomers to transiently knockdown tif2 gene, thus determining whether TIF2 plays a role in zebrafish early development.
Results:
We show that tif2 is involved in embryogenesis and in primitive hematopoiesis. tif2-knockdown zebrafish embryos are smaller than controls, they demonstrate shorter tails, they display notochord deformation and they exhibit U-shaped tail somites. A synthetic RNA encoding human TIF2 rescues the tif2-knockdown phenotype. Analysis of fli1 expression by whole-mount in situ hybridization indicates normal angioblast specification, but altered localization of intersomitic vessels. The posterior intermediate cell mass, in which a part of primitive hematopoiesis occurs, is altered in tif2 morphants and whole-mount in situ hybridization analyses of l-plastin and mpx expression suggest a specific inhibition of granulocytic and macrophagic differentiation at late stages.
Conclusion:
These data indicate an important role for TIF2 in zebrafish primitive myelopoiesis.
Insights
TIF2, a histone acetyl transferase (HAT), is crucial for zebrafish embryonic development and primitive hematopoiesis. Knocking down tif2 in zebrafish embryos results in developmental defects and impaired blood cell differentiation.
Area of Science:
- Developmental Biology
- Hematopoiesis
- Molecular Biology
Background:
- TIF2, a member of the p160 family, functions as a histone acetyl transferase (HAT).
- Previous studies in mice suggest potential overlapping functions among p160 family members.
- The zebrafish model was chosen to investigate TIF2's role in embryonic development due to its suitability for genetic studies.
Purpose of the Study:
- To characterize the role of TIF2, a histone acetyl transferase (HAT), during zebrafish embryonic development.
- To investigate the involvement of TIF2 in primitive hematopoiesis using a zebrafish model.
Main Methods:
- Transient knockdown of the tif2 gene in zebrafish embryos using antisense morpholino-modified oligomers.
- Phenotypic analysis of tif2-knockdown zebrafish embryos, including measurements of size, tail length, and notochord/somite morphology.
- Rescue experiments using synthetic RNA encoding human TIF2.
- Whole-mount in situ hybridization to analyze gene expression (fli1, l-plastin, mpx) and assess angioblast specification, vessel localization, and myeloid differentiation.
Main Results:
- TIF2 knockdown in zebrafish embryos leads to smaller size, shorter tails, notochord deformation, and U-shaped tail somites.
- The observed phenotype in tif2-knockdown embryos can be rescued by expressing human TIF2.
- While angioblast specification appears normal, the localization of intersomitic vessels is altered.
- TIF2 knockdown specifically inhibits granulocytic and macrophagic differentiation during late stages of primitive hematopoiesis.
Conclusions:
- TIF2 plays a significant role in zebrafish embryogenesis.
- TIF2 is essential for normal primitive myelopoiesis in zebrafish.
- These findings highlight TIF2's importance in regulating blood cell development.
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