ArticleThe Journal of experimental medicine2021
Stage-specific action of Runx1 and GATA3 controls silencing of PU.1 expression in mouse pro-T cells.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- Review
- Notch interaction with RUNX factors regulates initiation of the T-lineage program.The Journal of experimental medicine · 2026Article
- GATA3 regulates Th1/Th2 balance in allergic rhinitis by interacting with RUNX1.Future science OA · 2025Article
- A stem cell differentiation model reveals two alternative fates in CBFA2T3::GLIS2-driven acute megakaryoblastic leukemia initiation.Communications biology · 2025Article
- Ever-evolving insights into the cellular and molecular drivers of lymphoid cell development.Experimental hematology · 2024Review
- Unraveling the complex role of neutrophils in lymphoma: From pathogenesis to therapeutic approaches (Review).Molecular and clinical oncology · 2024Review
- Transcriptional network dynamics in early T cell development.The Journal of experimental medicine · 2024Review
- PU.1 and BCL11B sequentially cooperate with RUNX1 to anchor mSWI/SNF to poise the T cell effector landscape.Nature immunology · 2024Article
- T-cell commitment inheritance-an agent-based multi-scale model.NPJ systems biology and applications · 2024Article
- Intrinsically disordered domain of transcription factor TCF-1 is required for T cell developmental fidelity.Nature immunology · 2023Article
- Runx factors launch T cell and innate lymphoid programs via direct and gene network-based mechanisms.Nature immunology · 2023Article
- Short tandem repeats are important contributors to silencer elements in T cells.Nucleic acids research · 2023Article
- The Novel Structural Variation in the GHR Gene Is Associated with Growth Traits in Yaks (Animals : an open access journal from MDPI · 2023Article
- Multi-modular structure of the gene regulatory network for specification and commitment of murine T cells.Frontiers in immunology · 2023Review
- From thymus to tissues and tumors: A review of T-cell biology.The Journal of allergy and clinical immunology · 2023Review
- Liver group 2 innate lymphoid cells regulate blood glucose levels through IL-13 signaling and suppression of gluconeogenesis.Nature communications · 2022Article
- Regulation of the Signal-Dependent E Protein HEBAlt Through a YYY Motif Is Required for Progression Through T Cell Development.Frontiers in immunology · 2022Article
- LMO2 is essential to maintain the ability of progenitors to differentiate into T-cell lineage in mice.eLife · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
PU.1 (encoded by Spi1), an ETS-family transcription factor with many hematopoietic roles, is highly expressed in the earliest intrathymic T cell progenitors but must be down-regulated during T lineage commitment. The transcription factors Runx1 and GATA3 have been implicated in this Spi1 repression, but the basis of the timing was unknown. We show that increasing Runx1 and/or GATA3 down-regulates Spi1 expression in pro-T cells, while deletion of these factors after Spi1 down-regulation reactivates its expression. Leveraging the stage specificities of repression and transcription factor binding revealed an unconventional but functional site in Spi1 intron 2. Acute Cas9-mediated deletion or disruption of the Runx and GATA motifs in this element reactivates silenced Spi1 expression in a pro-T cell line, substantially more than disruption of other candidate elements, and counteracts the repression of Spi1 in primary pro-T cells during commitment. Thus, Runx1 and GATA3 work stage specifically through an intronic silencing element in mouse Spi1 to control strength and maintenance of Spi1 repression during T lineage commitment.
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Registered trials
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.