ArticleMolecular and cellular biology2000
Functions of E2A-HEB heterodimers in T-cell development revealed by a dominant negative mutation of HEB.
Article in Molecular and cellular biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed, 184 citations in OpenAlex.
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- Mapping putative enhancers in mouse oocytes and early embryos reveals TCF3/12 as key folliculogenesis regulators.Nature cell biology · 2024Article
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- Distinct requirements for Tcf3 and Tcf12 during oligodendrocyte development in the mouse telencephalon.Neural development · 2023Article
- Multi-modular structure of the gene regulatory network for specification and commitment of murine T cells.Frontiers in immunology · 2023Review
- Early Development of Innate Lymphoid Cells.Methods in molecular biology (Clifton, N.J.) · 2023Review
- Paxbp1 is indispensable for the survival of CD4 and CD8 double-positive thymocytes.Frontiers in immunology · 2023Article
- E-Protein Inhibition in ILC2 Development Shapes the Function of Mature ILC2s during Allergic Airway Inflammation.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- MonoallelicFrontiers in immunology · 2022Article
- The divergence between T cell and innate lymphoid cell fates controlled by E and Id proteins.Frontiers in immunology · 2022Review
- Transcriptional dynamics and epigenetic regulation of E and ID protein encoding genes during human T cell development.Frontiers in immunology · 2022Article
- Helix-Loop-Helix Proteins in Adaptive Immune Development.Frontiers in immunology · 2022Review
- E Protein Transcription Factors as Suppressors of T Lymphocyte Acute Lymphoblastic Leukemia.Frontiers in immunology · 2022Review
38 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Lymphocyte development and differentiation are regulated by the basic helix-loop-helix (bHLH) transcription factors encoded by the E2A and HEB genes. These bHLH proteins bind to E-box enhancers in the form of homodimers or heterodimers and, consequently, activate transcription of the target genes. E2A homodimers are the predominant bHLH proteins present in B-lineage cells and are shown genetically to play critical roles in B-cell development. E2A-HEB heterodimers, the major bHLH dimers found in thymocyte extracts, are thought to play a similar role in T-cell development. However, disruption of either the E2A or HEB gene led to only partial blocks in T-cell development. The exact role of E2A-HEB heterodimers and possibly the E2A and HEB homodimers in T-cell development cannot be distinguished in simple disruption analysis due to a functional compensation from the residual bHLH homodimers. To further define the function of E2A-HEB heterodimers, we generated and analyzed a dominant negative allele of HEB, which produces a physiological amount of HEB proteins capable of forming nonfunctional heterodimers with E2A proteins. Mice carrying this mutation show a stronger and earlier block in T-cell development than HEB complete knockout mice. The developmental block is specific to the alpha/beta T-cell lineage at a stage before the completion of V(D)J recombination at the TCRbeta gene locus. This defect is intrinsic to the T-cell lineage and cannot be rescued by expression of a functional T-cell receptor transgene. These results indicate that E2A-HEB heterodimers play obligatory roles both before and after TCRbeta gene rearrangement during the alpha/beta lineage T-cell development.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.