ArticleProceedings of the National Academy of Sciences of the United States of America2010
Compound haploinsufficiencies of Ebf1 and Runx1 genes impede B cell lineage progression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 52 citations in OpenAlex.
- B-lineage commitment is dependent on a reversible epigenetic switch.Genes & development · 2026Article
- Formation of the intestinal microbiota during mouse weaning promotes maturation of the IgA repertoire after growth.Bioscience of microbiota, food and health · 2025Article
- Early B-Cell Factor 1: An Archetype for a Lineage-Restricted Transcription Factor Linking Development to Disease.Advances in experimental medicine and biology · 2024Review
- Transcription factor networks link B-lymphocyte development and malignant transformation in leukemia.Genes & development · 2023Review
- Logic and lineage impacts on functional transcription factor deployment for T-cell fate commitment.Biophysical journal · 2021Review
- Loss ofOpen biology · 2018Article
- Molecular Regulation of Differentiation in Early B-Lymphocyte Development.International journal of molecular sciences · 2018Review
- Transcription Factor PU.1 Represses and Activates Gene Expression in Early T Cells by Redirecting Partner Transcription Factor Binding.Immunity · 2018Article
- Deregulation of kinase signaling and lymphoid development in EBF1-PDGFRB ALL leukemogenesis.Leukemia · 2018Article
- Spontaneous loss of B lineage transcription factors leads to pre-B leukemia in Ebf1Oncogenesis · 2017Article
- De Novo Mutations in EBF3 Cause a Neurodevelopmental Syndrome.American journal of human genetics · 2017Article
- MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis.Nature communications · 2016Article
- Zfp521 promotes B-cell viability and cyclin D1 gene expression in a B cell culture system.Leukemia research · 2016Article
- Hematopoiesis and T-cell specification as a model developmental system.Immunological reviews · 2016Review
- Transcription factor networks in B-cell differentiation link development to acute lymphoid leukemia.Blood · 2015Review
- Combined heterozygous loss of Ebf1 and Pax5 allows for T-lineage conversion of B cell progenitors.The Journal of experimental medicine · 2015Article
- The regulatory network of B-cell differentiation: a focused view of early B-cell factor 1 function.Immunological reviews · 2014Review
- Functionally responsive self-reactive B cells of low affinity express reduced levels of surface IgM.European journal of immunology · 2014Article
- Cell-intrinsic in vivo requirement for the E47-p21 pathway in long-term hematopoietic stem cells.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Transcriptional control of early T and B cell developmental choices.Annual review of immunology · 2014Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Early B cell factor (EBF)1 is essential for B lineage specification. Previously, we demonstrated the synergistic activation of Cd79a (mb-1) genes by EBF1 and its functional partner, RUNX1. Here, we identified consequences of Ebf1 haploinsufficiency together with haploinsufficiency of Runx1 genes in mice. Although numbers of "committed" pro-B cells were maintained in Ebf1(+/-)Runx1(+/-) (ER(het)) mice, activation of B cell-specific gene transcription was depressed in these cells. Expression of genes encoding Aiolos, kappa0 sterile transcripts, CD2 and CD25 were reduced and delayed in ER(het) pro-B cells, whereas surface expression of BP-1 was increased on late pro-B cells in ER(het) mice. Late pre-B and immature and mature B cells were decreased in the bone marrow of Ebf1(+/-) (E(het)) mice and were nearly absent in ER(het) mice. Although we did not observe significant effects of haploinsuficiencies on IgH or Igkappa rearrangements, a relative lack of Iglambda rearrangements was detected in E(het) and ER(het) pre-B cells. Together, these observations suggest that B cell lineage progression is impaired at multiple stages in the bone marrow of E(het) and ER(het) mice. Furthermore, enforced expression of EBF1 and RUNX1 in terminally differentiated plasmacytoma cells activated multiple early B cell-specific genes synergistically. Collectively, these studies illuminate the effects of reduced Ebf1 dosage and the compounding effects of reduced Runx1 dosage. Our data confirm and extend the importance of EBF1 in regulating target genes and Ig gene rearrangements necessary for B cell lineage specification, developmental progression, and homeostasis.
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