ArticleProceedings of the National Academy of Sciences of the United States of America2011
Transcription factor AP4 modulates reversible and epigenetic silencing of the Cd4 gene.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Heparan Sulfate Proteoglycans in Immunity.Proteoglycan research · 2026Article
- Enhancing the potency of CAR-T cells against solid tumors through transcription factor engineering.JCI insight · 2025Review
- Modular pooled discovery of synthetic knockin sequences to program durable cell therapies.Cell · 2023Article
- Combined inhibition of BET bromodomain and mTORC1/2 provides therapeutic advantage for rhabdomyosarcoma by switching cell death mechanism.Molecular carcinogenesis · 2022Article
- Article
- Review
- Discovery of gene regulatory elements through a new bioinformatics analysis of haploid genetic screens.PloS one · 2019Article
- Transcription factor activating protein 4 is synthetically lethal and a master regulator of MYCN-amplified neuroblastoma.Oncogene · 2018Article
- Tle corepressors are differentially partitioned to instruct CD8The Journal of experimental medicine · 2018Article
- Cutting Edge: The Histone Methyltransferase G9a Is Required for Silencing of Helper T Lineage-Associated Genes in Proliferating CD8 T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Identification of lineage-specifying cytokines that signal all CD8Nature immunology · 2017Article
- Heritable Gene Regulation in the CD4:CD8 T Cell Lineage Choice.Frontiers in immunology · 2017Review
- Comparative genetic screens in human cells reveal new regulatory mechanisms in WNT signaling.eLife · 2016Article
- The Transcription Factor AP4 Mediates Resolution of Chronic Viral Infection through Amplification of Germinal Center B Cell Responses.Immunity · 2016Article
- Myeloid zinc-finger 1 (MZF-1) suppresses prostate tumor growth through enforcing ferroportin-conducted iron egress.Oncogene · 2015Article
- c-Myc and AP4: a relay team for metabolic reprogramming of CD8+ T cells.Nature immunology · 2014Article
- c-Myc-induced transcription factor AP4 is required for host protection mediated by CD8+ T cells.Nature immunology · 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
- Dynamics of re-constitution of the human nuclear proteome after cell division is regulated by NLS-adjacent phosphorylation.Cell cycle (Georgetown, Tex.) · 2014Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
CD4 coreceptor expression is negatively regulated through activity of the Cd4 silencer in CD4(-)CD8(-) double-negative (DN) thymocytes and CD8(+) cytotoxic lineage T cells. Whereas Cd4 silencing is reversed during transition from DN to CD4(+)CD8(+) double-positive stages, it is maintained through heritable epigenetic processes following its establishment in mature CD8(+) T cells. We previously demonstrated that the Runx family of transcription factors is required for Cd4 silencing both in DN thymocytes and CD8(+) T cells. However, additional factors that cooperate with Runx proteins in the process of Cd4 silencing remain unknown. To identify collaborating factors, we used microarray and RNAi-based approaches and found the basic helix-loop-helix ZIP transcription factor AP4 to have an important role in Cd4 regulation. AP4 interacts with Runx1 in cells in which Cd4 is silenced, and is required for Cd4 silencing in immature DN thymocytes through binding to the proximal enhancer. Furthermore, although AP4-deficient CD8(+) T cells appeared to normally down-regulate CD4 expression, AP4 deficiency significantly increased the frequency of CD4-expressing effector/memory CD8(+) T cells in mice harboring point mutations in the Cd4 silencer. Our results suggest that AP4 contributes to Cd4 silencing both in DN and CD8(+) T cells by enforcing checkpoints for appropriate timing of CD4 expression and its epigenetic silencing.
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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.