title: Erythropoiesis is regulated by the transcription elongation factor Foggy/Spt5 through gata1 gene regulation.
abstract: Recent studies have showed that transcription elongation factors regulate early development. Foggy/Spt5 is a subunit of DRB sensitivity-inducing factor, which negatively and positively regulates transcription elongation. Here, we report that the positive function of Foggy/Spt5 is required for gata1 expression during zebrafish embryonic hematopoiesis. Antisense morpholino oligonucleotide (MO)-mediated knockdown of foggy/spt5 has led to a reduction in the expression of gata1 and the gata1 target genes alas2 and hbae3 and inhibited proper hemoglobin production. By contrast, expression of hematopoietic stem cell and endothelial markers, including scl, lmo2, gata2, fli-1, and flk-1, and expression of biklf, whose product directs gata1 expression via its direct binding to the gata1 promoter, were unaltered, suggesting that gata1 is a functionally important target gene of Foggy/Spt5. The MO-mediated gata1 repression was relieved by forced expression of wild-type foggy/spt5, but not by a mutant lacking the positive function. Therefore, this study provides evidence that Foggy/Spt5 plays an important role in gata1 gene expression and erythropoiesis through its transcriptional activation domain.
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Midori-ku, Yokohama, Kanagawa 226-8503, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Taneda
authors.forename: Wenyan
authors.initials: W
authors.lastname: Zhu
authors.forename: Qingfu
authors.initials: Q
authors.lastname: Cao
authors.forename: Hajime
authors.initials: H
authors.lastname: Watanabe
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Handa
authors.forename: Tadashi
authors.initials: T
authors.lastname: Wada
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins; D004920:Erythropoiesis / Q000235:genetics*; D050982:GATA1 Transcription Factor / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D016601:RNA-Binding Proteins; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics* / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D050982:GATA1 Transcription Factor; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C494691:gata1a protein, zebrafish; C416949:supt5h protein, zebrafish