ArticleMolecular and cellular biology2002
Gradient of E2A activity in B-cell development.
Article in Molecular and cellular biology, 2002. 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, 92 citations in OpenAlex.
- Unique chicken B cell development: species-specific mechanisms and contradictory requirements of B cell receptor for post-hatched B cell development.Frontiers in immunology · 2026Review
- Krüppel-like factor 4 control of immune cell function.Frontiers in immunology · 2025Review
- TCF3 haploinsufficiency defined by immune, clinical, gene-dosage, and murine studies.The Journal of allergy and clinical immunology · 2023Article
- MonoallelicFrontiers in immunology · 2022Article
- Sex bias in lymphocytes: Implications for autoimmune diseases.Frontiers in immunology · 2022Review
- Sex bias in autoimmunity.Current opinion in rheumatology · 2019Review
- 17β-Estradiol and 17α-Ethinyl Estradiol Exhibit Immunologic and Epigenetic Regulatory Effects in NZB/WF1 Female Mice.Endocrinology · 2019Article
- Paradoxical role of Id proteins in regulating tumorigenic potential of lymphoid cells.Frontiers of medicine · 2018Review
- Molecular processes involved in B cell acute lymphoblastic leukaemia.Cellular and molecular life sciences : CMLS · 2018Review
- Our Environment Shapes Us: The Importance of Environment and Sex Differences in Regulation of Autoantibody Production.Frontiers in immunology · 2018Review
- The miR-23a~27a~24-2 microRNA cluster buffers transcription and signaling pathways during hematopoiesis.PLoS genetics · 2017Article
- Bone marrow transcriptome and epigenome profiles of equine common variable immunodeficiency patients unveil block of B lymphocyte differentiation.Clinical immunology (Orlando, Fla.) · 2015Article
- SCL, LMO1 and Notch1 reprogram thymocytes into self-renewing cells.PLoS genetics · 2014Article
- The ID proteins: master regulators of cancer stem cells and tumour aggressiveness.Nature reviews. Cancer · 2014Review
- E2A predicts prognosis of colorectal cancer patients and regulates cancer cell growth by targeting miR-320a.PloS one · 2014Article
- Cell-intrinsic in vivo requirement for the E47-p21 pathway in long-term hematopoietic stem cells.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Cyclic AMP signaling inhibits megakaryocytic differentiation by targeting transcription factor 3 (E2A) cyclin-dependent kinase inhibitor 1A (CDKN1A) transcriptional axis.The Journal of biological chemistry · 2012Article
- Stage-specific functions of E-proteins at the β-selection and T-cell receptor checkpoints during thymocyte development.Immunologic research · 2011Article
- A tamoxifen inducible knock-in allele for investigation of E2A function.BMC developmental biology · 2009Article
- E47 controls the developmental integrity and cell cycle quiescence of multipotential hematopoietic progenitors.Journal of immunology (Baltimore, Md. : 1950) · 2008Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The E2A locus is a frequent target of chromosomal translocations in B-cell acute lymphoblastic leukemia (B-ALL). E2A encodes two products, E12 and E47, that are part of the basic helix-loop-helix (bHLH) family of transcription factors and are central in B lineage differentiation. E2A haplo-insufficiency hinders progression through three major checkpoints in B-cell development: commitment into the B lineage, at the pro-B to pre-B transition, and in the induction of immunoglobulin M (IgM) expression required for a functional BCR. These observations underscore the importance of E2A gene dosage in B-cell development. Here we show that a higher proportion of pro-B cells in E2A(+/-) mice is in the cell cycle compared to that in wild-type littermates. This increase correlates with lower p21(waf/cip1) levels, indicating that E2A has an antiproliferative function in B-cell progenitors. Ectopic expression in the B lineage of SCL/Tal1, a tissue-specific bHLH factor that inhibits E2A function, blocks commitment into the B lineage without affecting progression through later stages of differentiation. Furthermore, ectopic SCL expression exacerbates E2A haplo-insufficiency in B-cell differentiation, indicating that SCL genetically interacts with E2A. Taken together, these observations provide evidence for a gradient of E2A activity that increases from the pre-pro-B to the pre-B stage and suggest a model in which low levels of E2A (as in pro-B cells) are sufficient to control cell growth, while high levels (in pre-B cells) are required for cell differentiation. The antiproliferative function of E2A further suggests that in B-ALL associated with t(1;19) and t(17;19), the disruption of one E2A allele contributes to leukemogenesis, in addition to other anomalies induced by E2A fusion proteins.
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