| First Author | Okuno Y | Year | 2005 |
| Journal | Mol Cell Biol | Volume | 25 |
| Issue | 7 | Pages | 2832-45 |
| PubMed ID | 15767686 | Mgi Jnum | J:117409 |
| Mgi Id | MGI:3696365 | Doi | 10.1128/MCB.25.7.2832-2845.2005 |
| Citation | Okuno Y, et al. (2005) Potential autoregulation of transcription factor PU.1 by an upstream regulatory element. Mol Cell Biol 25(7):2832-45 |
| abstractText | 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. |
