ZFIN ID: ZDB-PUB-150407-2
Knockdown of transcription factor forkhead box O3 (FOXO3) suppresses erythroid differentiation in human cells and zebrafish
Wang, H., Li, Y., Wang, S., Zhang, Q., Zheng, J., Yang, Y., Qi, H., Qu, H., Zhang, Z., Liu, F., Fang, X.
Date: 2015
Source: Biochemical and Biophysical Research Communications   460(4): 923-30 (Journal)
Registered Authors: Liu, Feng, Wang, Hai
Keywords: FOXO3, erythroid differentiation, globin, zebrafish
Microarrays: GEO:GSE66860
MeSH Terms:
  • Animals
  • Base Sequence
  • Cell Differentiation/genetics*
  • Erythrocytes/cytology*
  • Female
  • Forkhead Transcription Factors/genetics
  • Forkhead Transcription Factors/metabolism
  • Forkhead Transcription Factors/physiology*
  • Gene Knockdown Techniques*
  • Humans
  • Male
  • Neoplasm Proteins/metabolism
  • RNA, Small Interfering/genetics
  • Transcriptome
  • Zebrafish
PubMed: 25843800 Full text @ Biochem. Biophys. Res. Commun.
Our previous study on the dynamic transcriptomes activated during human erythropoiesis suggested that transcription factor forkhead box O3 (FOXO3) possibly plays a role in erythroid differentiation. Functional studies in human cell line TF-1 indicated that FOXO3 knockdown repressed erythropoietin (EPO)-induced erythroid differentiation by activating promoter region of B-cell translocation gene 1 (BTG1), thereby regulating its expression. In zebrafish, injection of foxo3b-specific morpholinos (foxo3b MO) resulted in reduced globin (hbae1 and hbbe2) and gata1 gene expression. Transcriptome analyses of erythroid lineage cells isolated from the control and foxo3b morphants revealed the dynamic regulation of foxo3b. Further study suggested that BTG1 is partially responsible for FOXO3 regulation in erythroid differentiation of TF-1 cells but is inconsequential in zebrafish. Taken together, we found that FOXO3 plays an important role in erythroid differentiation in both human TF-1 cells and zebrafish, but the mechanism underlying this regulation still remains unclear.