Repression of Flt3 by Pax5 is crucial for B-cell lineage commitment.
Early B-lymphopoiesis requires the growth-factor receptors, IL-7R and Flt3, and the activity of a number of transcription factors. One factor, Pax5, is required for commitment to the B-cell lineage, although the molecular mechanism by which this occurs is unknown. We demonstrate here that an important function of Pax5 is to repress Flt3 transcription in B-cell progenitors, as Pax5-deficient pro-B cells express abundant Flt3 that is rapidly silenced upon the reintroduction of Pax5, whereas enforced expression of Flt3 in wild-type progenitors significantly impairs B-cell development. These findings demonstrate that the repression of Flt3 by Pax5 is essential for normal B-lymphopoiesis.
Holmes
Melissa L
ML
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.
Carotta
Sebastian
S
Corcoran
Lynn M
LM
Nutt
Stephen L
SL
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D002460:Cell Line; D019070:Cell Lineage; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D051379:Mice; D051757:PAX5 Transcription Factor / Q000378:metabolism / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3