Octamer binding factors and their coactivator can activate the murine PU.1 (spi-1) promoter.
PU.1 (spi-1), a member of the Ets transcription factor family, is predominantly expressed in myeloid and B cells, activates many B cell and myeloid genes, and is critical for development of both of these lineages. Our previous studies (Chen, H. M., Ray-Gallet, D., Zhang, P., Hetherington, C. J., Gonzalez, D. A., Zhang, D.-E., Moreau-Gachelin, F., and Tenen, D. G. (1995) Oncogene 11, 1549-1560) demonstrate that the PU.1 promoter directs cell type-specific reporter gene expression in myeloid cell lines, and that PU.1 activates its own promoter in an autoregulatory loop. Here we show that the murine PU.1 promoter is also specifically and highly functional in B cell lines as well. Oct-1 and Oct-2 can bind specifically to a site at base pair -55 in vitro, and this site is specifically protected in B cells in vivo. We also demonstrate that two other sites contribute to promoter activity in B cells; an Sp1 binding site adjacent to the octamer site, and the PU.1 autoregulatory site. Finally, we show that the B cell coactivator OBF-1/Bob1/OCA-B is only expressed in B cells and not in myeloid cells, and that OBF-1/Bob1/OCA-B can transactivate the PU.1 promoter in HeLa and myeloid cells. This B cell restricted coactivator may be responsible for the B cell specific expression of PU.1 mediated by the octamer site.
Chen
H
H
Hematology/Oncology Division, Department of Medicine, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
Zhang
P
P
Radomska
H S
HS
Hetherington
C J
CJ
Zhang
D E
DE
Tenen
D G
DG
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D001665:Binding Sites; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000502:physiology; D051863:Host Cell Factor C1; D006801:Humans; D051379:Mice; D050811:Octamer Transcription Factor-1; D050813:Octamer Transcription Factor-2; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D000099232:Proto-Oncogene Protein Spi-1
D017931:DNA Primers; D004268:DNA-Binding Proteins; D051863:Host Cell Factor C1; D050811:Octamer Transcription Factor-1; D050813:Octamer Transcription Factor-2; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; C497692:HCFC1 protein, human; C497693:Hcfc1 protein, mouse; C494165:POU2F1 protein, human; C058435:POU2F2 protein, human; C494166:Pou2f1 protein, mouse; C489206:Pou2f2 protein, mouse