Context-dependent function of "GATAswitch" sites in vivo

Jonathan W. Snow, Jennifer J. Trowbridge, Kirby D. Johnson, Tohru Fujiwara, Nikla E. Emambokus, Jeffrey A. Grass, Stuart H. Orkin, Emery H. Bresnick

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

Master transcriptional regulators of development often function through dispersed cis elements at endogenous target genes. While cis-elements are routinely studied in transfection and transgenic reporter assays, it is challenging to ascertain how they function in vivo. To address this problem in the context of the locus encoding the critical hematopoietic transcription factor Gata2, we engineered mice lacking a cluster of GATA motifs 2.8 kb upstream of the Gata2 transcriptional start site.We demonstrate that the -2.8 kb site confers maximal Gata2 expression in hematopoietic stem cells and specific hematopoietic progenitors. By contrast to our previous demonstration that a palindromic GATA motif at the neighboring -1.8 kb site maintains Gata2 repression in terminally differentiating erythroid cells, the -2.8 kb site was not required to initiate or maintain repression. These analyses reveal qualitatively distinct functions of 2 GATA motif-containing regions in vivo.

Original languageEnglish
Pages (from-to)4769-4772
Number of pages4
JournalBlood
Volume117
Issue number18
DOIs
Publication statusPublished - 2011 May 5
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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