title: Foxp1 is an essential transcriptional regulator of B cell development.
abstract: 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.
authors.affiliation: Department of Pathology, Harvard Medical School, CBR Institute for Biomedical Research, Boston, Massachusetts 02115, USA. hu@cbr.med.harvard.edu
authors.forename: Hui
authors.initials: H
authors.lastname: Hu
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Madhuri
authors.initials: M
authors.lastname: Borde
authors.forename: Julie
authors.initials: J
authors.lastname: Nardone
authors.forename: Shan
authors.initials: S
authors.lastname: Maika
authors.forename: Laura
authors.initials: L
authors.lastname: Allred
authors.forename: Philip W
authors.initials: PW
authors.lastname: Tucker
authors.forename: Anjana
authors.initials: A
authors.lastname: Rao
mesh_terms: 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*
chemical_list: D051858:Forkhead Transcription Factors; C432917:Foxp1 protein, mouse; D012097:Repressor Proteins