Potential autoregulation of transcription factor PU.1 by an upstream regulatory element

Yutaka Okuno, Gang Huang, Frank Rosenbauer, Erica K. Evans, Hanna S. Radomska, Hiromi Iwasaki, Koichi Akashi, Francoise Moreau-Gachelin, Youlin Li, Pu Zhang, Berthold Göttgens, Daniel G. Tenen

Research output: Contribution to journalArticlepeer-review

125 Citations (Scopus)

Abstract

Regulation of the hematopoietic transcription factor PU.1 (Spi-1) plays a critical role in the development of white cells, and abnormal expression of PU.1 can lead to leukemia. We previously reported that the PU.1 promoter cannot induce expression of a reporter gene in vivo, and cell-type-specific expression of PU.1 in stable lines was conferred by a 3.4-kb DNA fragment including a DNase I hypersensitive site located 14 kb upstream of the transcription start site. Here we demonstrate that this kb -14 site confers lineage-specific reporter gene expression in vivo. This kb -14 upstream regulatory element contains two 300-bp regions which are highly conserved in five mammalian species. In Friend virus-induced erythroleukemia, the spleen focus-forming virus integrates into the PU.1 locus between these two conserved regions. DNA binding experiments demonstrated that PU.1 itself and Elf-1 bind to a highly conserved site within the proximal homologous region in vivo. A mutation of this site abolishing binding of PU.1 and Elf-1 led to a marked decrease in the ability of this upstream element to direct activity of reporter gene in myelomonocytic cell lines. These data suggest that a potential positive autoregulatory loop mediated through an upstream regulatory element is essential for proper PU.1 gene expression.

Original languageEnglish
Pages (from-to)2832-2845
Number of pages14
JournalMolecular and cellular biology
Volume25
Issue number7
DOIs
Publication statusPublished - Apr 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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