Erythropoiesis is regulated by the transcription elongation factor Foggy/Spt5 through gata1 gene regulation

Genes Cells. 2011 Feb;16(2):231-42. doi: 10.1111/j.1365-2443.2010.01481.x. Epub 2011 Jan 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • DNA-Binding Proteins
  • Erythropoiesis / genetics*
  • GATA1 Transcription Factor / genetics*
  • Gene Expression Regulation, Developmental*
  • Hematopoietic Stem Cells / metabolism
  • Molecular Sequence Data
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • RNA-Binding Proteins
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Zebrafish / embryology*
  • Zebrafish / genetics
  • Zebrafish Proteins / genetics*
  • Zebrafish Proteins / physiology*

Substances

  • DNA-Binding Proteins
  • GATA1 Transcription Factor
  • Nuclear Proteins
  • RNA-Binding Proteins
  • Transcription Factors
  • Zebrafish Proteins
  • gata1a protein, zebrafish
  • supt5h protein, zebrafish