Requirement of Transcription Factor PU.1 in the Development of Multiple Hematopoietic Lineages

Abstract

The transcription factor PU.1 is a hematopoietic-specific member of the ets family. Mice carrying a mutation in the PU.1 locus were generated by gene targeting. Homozygous mutant embryos died at a late gestational stage. Mutant embryos produced normal numbers of megakaryocytes and erythroid progenitors, but some showed an impairment of erythroblast maturation. An invariant consequence of the mutation was a multilineage defect in the generation of progenitors for B and T lymphocytes, monocytes, and granulocytes. Thus, the developmental programs of lymphoid and myeloid lineages require a common genetic function likely acting at the level of a multipotential progenitor.

GOOSECOID inhibits erythrocyte differentiation by competing with Rb for PU.1 binding in murine cells

“…Several lines of evidence indicate that PU.1 plays an important role in embryonic blood formation. One strain of PU.1 knock out mice shows defects in erythroid maturation (Scott et al, 1994). Another PU.1 de®cient mouse strain exhibits no apparent defects in erythrocyte development but are de®cient in macrophages, neutrophils, B cells, and T cells compared to wild-type mice (McKercher et al, 1996;Scott et al, 1997).…”

“…Vector transfected (Vector) and four individual clones (gsc74-1 ± 4) were cultured in the presence or absence of activin (100 ng/ml) for 6 days at 1610 3 cells/100 ml/well in a 96-well microplate. After 6 days, cultures were stained with dianisidine to detect hemoglobin positive cells (Eto et al, 1987) ets family protein PU.1 (Klemsz et al, 1990;Hagemeier et al, 1993) with a molecular weight between 36 and 46 kDa (Schuetze et al, 1992;Scott et al, 1994). To investigate a possible interaction of PU.1 and GSC, lysates from metabolically labeled F5-5 cells from both untreated and activin stimulated cultures were subjected to sequential a nity chromatography on GST-GSC beads, followed by immunoprecipitation of eluted material with an anti-PU.1 antibody.…”

A novel transcription factor, ELF5, belongs to the ELF subfamily of ETS genes and maps to human chromosome 11p13–15, a region subject to LOH and rearrangement in human carcinoma cell lines

“…Many ETS factors have been implicated in the control of cellular proliferation and tumorigenesis (Seth et al, 1992;Macleod et al, 1992;Wasylyk et al, 1993;Janknecht and Nordheim, 1993;Scott et al, 1994a;Muthusamy et al, 1995). ETS1, ETS2, ERG2 and PU.1 are proto-oncogenes with mitogenic and transforming activity when overexpressed in ®broblasts (Seth et al, 1989;Seth and Papas, 1990;Hart et al, 1995;Moreau-Gachelin et al, 1996).…”

Isolation and characterization of a chicken homologue of the Spi-1/PU.1 transcription factor

“…These results and others (Rao et al, 1997) strongly suggest that downregulation of Spi-1/PU.1 is a prerequisite to terminal di erentiation of erythroid cells. Homologous recombination of Spi-1/PU.1 gene in mouse leads to the death at embryonic stage (Scott et al, 1994) or days after birth (McKercher et al, 1996). The homozygous mutant embryos show a multilineage defect in the maturation of B and T lymphocytes, macrophages and neutrophils.…”