ArticleJournal of immunology (Baltimore, Md. : 1950)2014
A silencer-proximal intronic region is required for sustained CD4 expression in postselection thymocytes.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- A conserved element in the first intron ofFrontiers in immunology · 2024Article
- The Association between Deoxyribonucleic Acid Hypermethylation in Intron VII and Human Leukocyte Antigen-CInternational journal of clinical practice · 2023Article
- Epigenetic Reprogramming Leads to Downregulation of CD4 and Functional Changes in African Green Monkey Memory CD4Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- NuRD complex recruitment to Thpok mediates CD4Science immunology · 2022Article
- CD4 expression in effector T cells depends on DNA demethylation over a developmentally established stimulus-responsive element.Nature communications · 2022Article
- Deciphering the Complexity of 3D Chromatin Organization Driving Lymphopoiesis and Lymphoid Malignancies.Frontiers in immunology · 2021Review
- Epigenetic silencing of CD4 expression in nonpathogenic SIV infection in African green monkeys.JCI insight · 2020Article
- TheJournal of clinical medicine · 2019Article
- The histone chaperone CAF-1 cooperates with the DNA methyltransferases to maintainGenes & development · 2019Article
- Stage-specific epigenetic regulation of CD4 expression by coordinated enhancer elements during T cell development.Nature communications · 2018Article
- Runx-dependent and silencer-independent repression of a maturation enhancer in the Cd4 gene.Nature communications · 2018Article
- Heritable Gene Regulation in the CD4:CD8 T Cell Lineage Choice.Frontiers in immunology · 2017Review
- What Happens in the Thymus Does Not Stay in the Thymus: How T Cells Recycle the CD4+-CD8+ Lineage Commitment Transcriptional Circuitry To Control Their Function.Journal of immunology (Baltimore, Md. : 1950) · 2016Review
- Tcf1 and Lef1 pack their own HDAC.Nature immunology · 2016Article
- Regulation of DNA methylation dictates Cd4 expression during the development of helper and cytotoxic T cell lineages.Nature immunology · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
It has been proposed that differential kinetics of CD4/CD8 coreceptors regulate fate choice of selected thymocytes. Sustained signals by interaction between MHC class II and TCR/CD4 is required for commitment to the CD4 helper lineage. Although prematurely terminated MHC-TCR/CD4 interaction in transgenic mouse models results in lineage redirection, it is unclear whether CD4 expression is actively maintained by endogenous cis-elements to facilitate prolonged signaling under physiological conditions. In this article, we show that sustained CD4 expression in postselection thymocytes requires an intronic sequence containing an uncharacterized DNase I hypersensitivity (DHS) site located 3' to the silencer. Despite normal CD4 expression before selection, thymocytes lacking a 1.5-kb sequence in intron 1 including the 0.4-kb silencer and the DHS, but not the 0.4-kb silencer alone, failed to maintain CD4 expression upon positive selection and are redirected to the CD8 lineage after MHC class II-restricted selection. Furthermore, CpG dinucleotides adjacent to the DHS are hypermethylated in CD8(+) T cells. These results indicate that the 1.5-kb cis-element is required in postselection thymocytes for helper lineage commitment, presumably mediating the maintenance of CD4 expression, and suggest that inactivation of the cis-element by DNA methylation may contribute to epigenetic Cd4 silencing.
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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.