title: EBF1 is essential for B-lineage priming and establishment of a transcription factor network in common lymphoid progenitors.
abstract: Development of B-lymphoid cells in the bone marrow is a process under strict control of a hierarchy of transcription factors. To understand the development of a B-lymphoid-restricted functional network of transcription factors, we have investigated the cell autonomous role of the transcription factor EBF1 in early B cell development. This revealed that even though transplanted EBF1-deficient fetal liver cells were able to generate common lymphoid progenitors (CLPs) as well as B220(+)CD43(+)AA4.1(+) candidate precursor B cells, none of these populations showed signs of B lineage priming. The isolated CLPs were able to generate T lymphocytes in vitro supporting the idea that the phenotype of EBF1-deficient mice is restricted to the development of the B lineage. Furthermore, EBF deficient CLPs displayed a reduction in Ig H chain recombination as compared with their wild-type counterpart and essentially lacked transcription of B-lineage-associated genes. Among the genes displaying reduced expression in the EBF1 deficient CLPs were the transcription factors Pax5, Pou2af1 (OcaB), and FoxO1 that all appear to be direct genetic targets for EBF1 because their promoters contained functional binding sites for this factor. This leads us to suggest that EBF1 regulates a transcription factor network crucial for B lineage commitment.
authors: Department for Biomedicin and Surgery, Linköping University, Sweden.
authors: Sasan
authors: S
authors: Zandi
authors: Robert
authors: R
authors: Mansson
authors: Panagiotis
authors: P
authors: Tsapogas
authors: Jenny
authors: J
authors: Zetterblad
authors: David
authors: D
authors: Bryder
authors: Mikael
authors: M
authors: Sigvardsson
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D019070:Cell Lineage; D015536:Down-Regulation; D053263:Gene Regulatory Networks; D054503:Lymphoid Progenitor Cells / Q000166:cytology*; D051379:Mice; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics
chemical_list: C489921:Ebf1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors