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

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.

• Authors: 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
• Journal: Molecular and cellular biology (Mol Cell Biol) Vol. 25 Issue 7 Pg. 2832-45 (Apr 2005) ISSN: 0270-7306 [Print] United States
• PMID: 15767686 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Proto-Oncogene Proteins
• Trans-Activators
• proto-oncogene protein Spi-1

Topics

• Animals
• B-Lymphocytes (metabolism)
• Base Sequence
• Binding Sites
• Cell Lineage
• Gene Expression Regulation (genetics)
• Humans
• Mice
• Mice, Transgenic
• Molecular Sequence Data
• Mutation (genetics)
• Myeloid Cells (metabolism)
• Organ Specificity
• Proto-Oncogene Proteins (genetics, metabolism)
• Response Elements (genetics)
• Sequence Alignment
• Trans-Activators (genetics, metabolism)