title: Knockdown of transcription factor forkhead box O3 (FOXO3) suppresses erythroid differentiation in human cells and zebrafish.
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.
authors.affiliation: 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.
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Yanming
authors.initials: Y
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Sifeng
authors.initials: S
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Jiawen
authors.initials: J
authors.lastname: Zheng
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Heyuan
authors.initials: H
authors.lastname: Qi
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Hongzhu
authors.initials: H
authors.lastname: Qu
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: liuf@ioz.ac.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Fang
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics*; D004912:Erythrocytes / Q000166:cytology*; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D059467:Transcriptome; D015027:Zebrafish
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C074086:BTG1 protein, human
keywords: Erythroid differentiation; FOXO3; Globin; Zebrafish