Foxp1 is an essential transcriptional regulator of B cell development.
Forkhead transcription factors are key participants in development and immune regulation. Here we demonstrate that absence of the gene encoding the forkhead transcription factor Foxp1 resulted in a profound defect in early B cell development. Foxp1 deficiency was associated with decreased expression of all B lineage genes in B220+ fetal liver cells as well as with a block in the transition from pro-B cell to pre-B cell involving diminished expression of recombination-activating genes 1 and 2. Foxp1 bound to the Erag enhancer and was involved in controlling variable-(diversity)-joining recombination of the gene encoding immunoglobulin heavy chain in a B cell lineage-specific way. Our results identify Foxp1 as an essential participant in the transcriptional regulatory network of B lymphopoiesis.
Hu
Hui
H
Department of Pathology, Harvard Medical School, CBR Institute for Biomedical Research, Boston, Massachusetts 02115, USA. hu@cbr.med.harvard.edu
Wang
Bin
B
Borde
Madhuri
M
Nardone
Julie
J
Maika
Shan
S
Allred
Laura
L
Tucker
Philip W
PW
Rao
Anjana
A
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D001483:Base Sequence; D015139:Blotting, Southern; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology*; D002678:Chimera; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology*; D015870:Gene Expression; D016654:Genes, RAG-1 / Q000276:immunology; D006801:Humans; D038041:Lymphopoiesis / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D012097:Repressor Proteins / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic / Q000276:immunology*
D051858:Forkhead Transcription Factors; C432917:Foxp1 protein, mouse; D012097:Repressor Proteins