Regulation of B lymphocyte and macrophage development by graded expression of PU. 1

RP DeKoter, H Singh - Science, 2000 - science.org
Science, 2000science.org
The ets family transcription factor PU. 1 is required for the development of multiple lineages
of the immune system. Using retroviral transduction of PU. 1 complementary DNA into
mutant hematopoietic progenitors, we demonstrate that differing concentrations of the
protein regulate the development of B lymphocytes as compared with macrophages. A low
concentration of PU. 1 protein induces the B cell fate, whereas a high concentration
promotes macrophage differentiation and blocks B cell development. Conversely, a …
The ets family transcription factor PU.1 is required for the development of multiple lineages of the immune system. Using retroviral transduction of PU.1 complementary DNA into mutant hematopoietic progenitors, we demonstrate that differing concentrations of the protein regulate the development of B lymphocytes as compared with macrophages. A low concentration of PU.1 protein induces the B cell fate, whereas a high concentration promotes macrophage differentiation and blocks B cell development. Conversely, a transcriptionally weakened mutant protein preferentially induces B cell generation. Our results suggest that graded expression of a transcription factor can be used to specify distinct cell fates in the hematopoietic system.
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