PU.1 regulates expression of the interleukin-7 receptor in lymphoid progenitors.
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.
DeKoter
Rodney P
RP
Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, The University of Chicago, 5841 S. Maryland Ave., MC1028, Chicago, IL 60637, USA.
Lee
Hyun-Jun
HJ
Singh
Harinder
H
D016475:3T3 Cells; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D020395:Receptors, Interleukin-7 / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000502:physiology; D012190:Retroviridae; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic; D014161:Transduction, Genetic; D000099232:Proto-Oncogene Protein Spi-1
D004268:DNA-Binding Proteins; D015851:Interleukin-7; D011518:Proto-Oncogene Proteins; D020395:Receptors, Interleukin-7; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; C076877:SPIB protein, human