title: Progenitor stage-specific activity of a cis-acting double GATA motif for Gata1 gene expression.
abstract: GATA1 is a master regulator of erythropoiesis, expression of which is regulated by multiple discrete cis-acting elements. In this study, we examine the activity of a promoter-proximal double GATA (dbGATA) motif, using a Gata1 bacterial artificial chromosome (BAC)-transgenic green fluorescent protein (GFP) reporter (G1BAC-GFP) mouse system. Deletion of the dbGATA motif led to significant reductions in GFP expression in hematopoietic progenitors, while GFP expression was maintained in erythroblasts. Consistently, in mice with a germ line deletion of the dbGATA motif (Gata1(ΔdbGATA) mice), GATA1 expression in progenitors was significantly decreased. The suppressed GATA1 expression was associated with a compensatory increase in GATA2 levels in progenitors. When we crossed Gata1(ΔdbGATA) mice with Gata2 hypomorphic mutant mice (Gata2(fGN/fGN) mice), the Gata1(ΔdbGATA)::Gata2(fGN/fGN) compound mutant mice succumbed to a significant decrease in the progenitor population, whereas both groups of single mutant mice maintained progenitors and survived to adulthood, indicating the functional redundancy between GATA1 and GATA2 in progenitors. Meanwhile, the effects of the dbGATA site deletion on Gata1 expression were subtle in erythroblasts, which showed increased GATA1 binding and enhanced accumulation of active histone marks around the 1st-intron GATA motif of the ΔdbGATA locus. These results thus reveal a novel role of the dbGATA motif in the maintenance of Gata1 expression in hematopoietic progenitors and a functional compensation between the dbGATA site and the 1st-intron GATA motif in erythroblasts.
authors.affiliation: Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan moriguch@med.tohoku.ac.jp masiyamamoto@med.tohoku.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Moriguchi
authors.affiliation: Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Mikiko
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Takai
authors.affiliation: Department of Pharmacy, Takasaki University of Health and Welfare, Takasaki, Japan.
authors.forename: Kinuko
authors.initials: K
authors.lastname: Ohneda
authors.affiliation: Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan moriguch@med.tohoku.ac.jp masiyamamoto@med.tohoku.ac.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D000483:Alleles; D020816:Amino Acid Motifs; D000818:Animals; D002469:Cell Separation; D047369:Chromatin Immunoprecipitation; D022202:Chromosomes, Artificial, Bacterial; D004900:Erythroblasts / Q000166:cytology*; D004920:Erythropoiesis; D005260:Female; D005434:Flow Cytometry; D050982:GATA1 Transcription Factor / Q000378:metabolism*; D050989:GATA2 Transcription Factor / Q000378:metabolism; D017353:Gene Deletion; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006706:Homeostasis; D007438:Introns; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D011485:Protein Binding
chemical_list: D050982:GATA1 Transcription Factor; D050989:GATA2 Transcription Factor; D049452:Green Fluorescent Proteins