title: GATA-1 transcription is controlled by distinct regulatory mechanisms during primitive and definitive erythropoiesis.
abstract: Transcription factor GATA-1 is required for the terminal differentiation of both the primitive and definitive erythroid cell lineages, and yet the regulatory mechanisms of GATA-1 itself are not well understood. To clarify how the GATA-1 gene is transcriptionally controlled in vivo, presumptive regulatory regions of the gene were tested by fusion to a reporter gene and then examined in transgenic mice. We found that a transcriptional control element located between -3.9 and -2.6 kb 5' to the erythroid first exon serves as an activating element and that this sequence alone is sufficient to recapitulate the expression of GATA-1 (but uniquely in primitive erythroid cells). Addition of sequences from the GATA-1 first intron to this upstream element provides a necessary and sufficient condition for complete recapitulation of GATA-1 expression in both primitive and definitive erythroid cells. The first intron element does not possess intrinsic transcriptional activation potential when linked to the GATA-1 gene promoter but rather requires the upstream activating element for its activity. These experiments show that GATA-1 gene expression is regulated by discrete transcriptional control elements during definitive and primitive erythropoiesis: The 5' element displays properties anticipated for a primitive erythroid cell-specific activating element, and the novel element within the GATA-1 first intron specifically augments this activity in definitive erythroid cells.
authors.affiliation: Department of Biochemistry, Tohoku University School of Medicine, Sendai 980-77, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Onodera
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: S
authors.initials: S
authors.lastname: Nishimura
authors.forename: J
authors.initials: J
authors.lastname: Ohta
authors.forename: H
authors.initials: H
authors.lastname: Motohashi
authors.forename: K
authors.initials: K
authors.lastname: Yomogida
authors.forename: N
authors.initials: N
authors.lastname: Hayashi
authors.forename: J D
authors.initials: JD
authors.lastname: Engel
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005314:Embryonic and Fetal Development; D015672:Erythroid Precursor Cells; D050981:Erythroid-Specific DNA-Binding Factors; D004920:Erythropoiesis / Q000235:genetics*; D050982:GATA1 Transcription Factor; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000096:biosynthesis*; D014158:Transcription, Genetic; D015017:Yolk Sac
chemical_list: D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D014157:Transcription Factors