ArticleGenes & development2010
Epigenetic propagation of CD4 expression is established by the Cd4 proximal enhancer in helper T cells.
Article in Genes & development, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 62 citations in OpenAlex.
- PET-based immunomapping of intratumoral CD4Science advances · 2025Article
- The TET-TDG axis in T cells and biological processes.International immunology · 2025Review
- A Bcl11bFrontiers in immunology · 2024Article
- 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
- Transcriptional Regulation of Early T-Lymphocyte Development in Thymus.Frontiers in immunology · 2022Review
- Single-cell profiling of microenvironment components by spatial localization in pancreatic ductal adenocarcinoma.Theranostics · 2022Article
- In search of lost time: Enhancers as modulators of timing in lymphocyte development and differentiation.Immunological reviews · 2021Review
- Epigenetic silencing of CD4 expression in nonpathogenic SIV infection in African green monkeys.JCI insight · 2020Article
- 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
- Super-enhancers: Asset management in immune cell genomes.Trends in immunology · 2015Review
- Regulation of DNA methylation dictates Cd4 expression during the development of helper and cytotoxic T cell lineages.Nature immunology · 2015Article
- The microRNA biogenesis machinery modulates lineage commitment during αβ T cell development.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Genome-wide and single-cell analyses reveal a context dependent relationship between CBP recruitment and gene expression.Nucleic acids research · 2014Article
- LMO2 induces T-cell leukemia with epigenetic deregulation of CD4.Experimental hematology · 2014Article
- A silencer-proximal intronic region is required for sustained CD4 expression in postselection thymocytes.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
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6 authors at 1 institution in 1 country.
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Abstract
The stability of a lineage program (cellular memory) is dependent on mechanisms that epigenetically maintain active or repressed states of gene expression (transcriptional memory). Although epigenetic silencing of genes has been clearly demonstrated from yeast to mammals, heritable maintenance of active transcription has been less clearly defined. To investigate the potential role of active transcriptional memory during lineage diversification, we employed targeted mutation of a positive-acting cis element in the Cd4 locus to determine the impact on CD4 expression and the differentiation of CD4(+) helper T cells in mice. We show that the proximal enhancer (E4(P)) of Cd4 is essential for CD4 expression in immature CD4(+)8(+) thymocytes. Furthermore, its loss resulted in reduced and unstable expression of CD4 in mature T cells. However, if the enhancer was deleted after cells had already committed to the helper T-cell lineage, CD4 expression remained high and was stable upon cell division. "Active" histone modifications, once initiated by E4(P), were also propagated independently of the enhancer. Thus, E4(P) is responsible for establishing an epigenetically inherited active Cd4 locus in the helper T-cell lineage. To our knowledge, this is the first genetic demonstration of active transcriptional memory in mammalian cells.
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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.