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PU.1 regulates expression of the interleukin-7 receptor in lymphoid progenitors
Rodney P DeKoter1, Hyun-Jun Lee, Harinder Singh
1Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, The University of Chicago, 5841 S. Maryland Ave., MC1028, Chicago, IL 60637, USA.
Abstract:
Development of the lymphoid system is dependent on the Ets family transcription factor PU.1. We demonstrate that PU.1(-/-) hematopoietic progenitors fail to express IL-7Ralpha transcripts. Promoter and chromatin crosslinking analyses suggest that PU.1 directly regulates transcription of the IL-7Ralpha gene. Retroviral transduction of IL-7Ralpha into PU.1(-/-) progenitors restores IL-7-dependent proliferation and induces, at low frequency, the generation of pro-B cells undergoing an apparently normal program of differentiation. Although the related factor Spi-B can substitute for PU.1 in early B cell development, it is not required. These results demonstrate that PU.1 functions to regulate early B cell development in part by controlling the expression of the IL-7Ralpha gene.