Progenitor stage-specific activity of a cis-acting double GATA motif for Gata1 gene expression

Takashi Moriguchi, Mikiko Suzuki, Lei Yu, Jun Takai, Kinuko Ohneda, Masayuki Yamamoto

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

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 (Gata1ΔdbGATA 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 Gata1ΔdbGATA mice with Gata2 hypomorphic mutant mice (Gata2fGN/fGN mice), the Gata1ΔdbGATA::Gata2fGN/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 1stintron 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.

Original languageEnglish
Pages (from-to)805-815
Number of pages11
JournalMolecular and cellular biology
Volume35
Issue number5
DOIs
Publication statusPublished - 2015

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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