PU.1 exhibits partial functional redundancy with Spi-B, but not with Ets-1 or Elf-1.
Previously it was shown that the Ets proteins, PU.1 and Spi-B, exhibit functional redundancy in B lymphocytes. To investigate the possibility that PU.1 or Spi-B or both share overlapping roles with Ets-1 or Elf-1, PU.1(+/-)Ets-1(-/-), PU.1(+/-)Elf-1(-/-), and Spi-B(-/-)Ets-1(-/-) animals were generated. No blood cell defects were observed in these animals except those previously reported for Ets-1(-/-) mice. Therefore, no genetic overlap was detected between PU.1 or Spi-B with Ets-1 or Elf-1. In contrast, the results confirmed functional redundancy for PU.1 and Spi-B in that PU.1(+/-)Spi-B(-/-) bone marrow progenitors yielded smaller colonies in methylcellulose cultures than did wild-type, PU.1(+/-) or Spi-B(-/-) progenitors. In addition, PU.1(+/-)Spi-B(+/+), PU.1(+/-)Spi-B(+/-), and PU.1(+/-) Spi-B(-/-) mice displayed extramedullary splenic hematopoiesis. In summary, PU.1 and Spi-B regulate common target genes required for proliferation of hematopoietic progenitors or their committed descendants, whereas Ets-1 or Elf-1 do not appear to regulate shared target genes with PU.1 or Spi-B.
Garrett-Sinha
L A
LA
Department of Medicine and Pathology, University of Chicago, IL, USA.
Dahl
R
R
Rao
S
S
Barton
K P
KP
Simon
M C
MC
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology; D051379:Mice; D009687:Nuclear Proteins; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology*; D050783:Proto-Oncogene Proteins c-ets; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*; D000099232:Proto-Oncogene Protein Spi-1
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; C512897:ELF1 protein, human; C494041:ETS1 protein, human; C512896:Elf1 protein, mouse; C494042:Ets1 protein, mouse; C076877:SPIB protein, human