Knockdown of transcription factor forkhead box O3 (FOXO3) suppresses erythroid differentiation in human cells and zebrafish

Hai Wang; Yanming Li; Sifeng Wang; Qian Zhang; Jiawen Zheng; Yadong Yang; Heyuan Qi; Hongzhu Qu; Zhaojun Zhang; Feng Liu; Xiangdong Fang

doi:10.1016/j.bbrc.2015.03.128

Knockdown of transcription factor forkhead box O3 (FOXO3) suppresses erythroid differentiation in human cells and zebrafish

Biochem Biophys Res Commun. 2015 May 15;460(4):923-30. doi: 10.1016/j.bbrc.2015.03.128. Epub 2015 Apr 3.

Authors

Hai Wang¹, Yanming Li², Sifeng Wang³, Qian Zhang⁴, Jiawen Zheng², Yadong Yang⁴, Heyuan Qi², Hongzhu Qu⁴, Zhaojun Zhang⁴, Feng Liu⁵, Xiangdong Fang⁶

Affiliations

¹ CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; China National Committee for Terms in Sciences and Technologies, Beijing 100717, China.
² CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
³ State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
⁴ CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
⁵ State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: liuf@ioz.ac.cn.
⁶ CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: fangxd@big.ac.cn.

PMID: 25843800
DOI: 10.1016/j.bbrc.2015.03.128

Abstract

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.

Keywords: Erythroid differentiation; FOXO3; Globin; Zebrafish.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Base Sequence
Cell Differentiation / genetics*
Erythrocytes / cytology*
Female
Forkhead Box Protein O3
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

Substances

FOXO3 protein, human
Forkhead Box Protein O3
Forkhead Transcription Factors
Neoplasm Proteins
RNA, Small Interfering
BTG1 protein, human