A lineage-specific transcriptional silencer regulates CD4 gene expression during T lymphocyte development - PubMed (original) (raw)
A lineage-specific transcriptional silencer regulates CD4 gene expression during T lymphocyte development
S Sawada et al. Cell. 1994.
Abstract
During development of T lymphocytes, differential regulation of expression of the CD4 and CD8 glycoproteins is coupled to the choice of one of two pathways of differentiation. Thymocytes that express both of these coreceptors commit to either the helper lineage, shutting off CD8, or the cytotoxic lineage, shutting off CD4. We have used transgenic mice to identify an intronic regulatory region that controls CD4 gene expression during development. This region selectively extinguishes transgene expression in CD4-CD8+, but not CD4+CD8- nor CD4+CD8+ T cells. It also represses gene expression in CD4-CD8- immature thymocytes, indicating that the CD4 gene is derepressed during differentiation from the CD4-CD8- to the CD4+CD8+ stage. The negative element(s) is both orientation and position independent and acts also on heterologous regulatory sequences. Its properties are functionally similar to those of silencers described in yeast and in Drosophila, suggesting that we have identified a developmentally regulated vertebrate transcriptional silencer.
Similar articles
- Specific expression of the human CD4 gene in mature CD4+ CD8- and immature CD4+ CD8+ T cells and in macrophages of transgenic mice.
Hanna Z, Simard C, Laperrière A, Jolicoeur P. Hanna Z, et al. Mol Cell Biol. 1994 Feb;14(2):1084-94. doi: 10.1128/mcb.14.2.1084-1094.1994. Mol Cell Biol. 1994. PMID: 8289789 Free PMC article. - Morpholino antisense oligonucleotide-mediated gene knockdown during thymocyte development reveals role for Runx3 transcription factor in CD4 silencing during development of CD4-/CD8+ thymocytes.
Ehlers M, Laule-Kilian K, Petter M, Aldrian CJ, Grueter B, Würch A, Yoshida N, Watanabe T, Satake M, Steimle V. Ehlers M, et al. J Immunol. 2003 Oct 1;171(7):3594-604. doi: 10.4049/jimmunol.171.7.3594. J Immunol. 2003. PMID: 14500656 - Thymocytes control the CD4 gene differently from mature T lymphocytes.
Uematsu Y, Donda A, De Libero G. Uematsu Y, et al. Int Immunol. 1997 Jan;9(1):179-87. doi: 10.1093/intimm/9.1.179. Int Immunol. 1997. PMID: 9043959 - The regulation of CD4 and CD8 coreceptor gene expression during T cell development.
Ellmeier W, Sawada S, Littman DR. Ellmeier W, et al. Annu Rev Immunol. 1999;17:523-54. doi: 10.1146/annurev.immunol.17.1.523. Annu Rev Immunol. 1999. PMID: 10358767 Review. - The regulation and function of the CD4 coreceptor during T lymphocyte development.
Killeen N, Littman DR. Killeen N, et al. Curr Top Microbiol Immunol. 1996;205:89-106. doi: 10.1007/978-3-642-79798-9_5. Curr Top Microbiol Immunol. 1996. PMID: 8575199 Review.
Cited by
- DEPDC5 protects CD8+ T cells from ferroptosis by limiting mTORC1-mediated purine catabolism.
Li S, Ouyang X, Sun H, Jin J, Chen Y, Li L, Wang Q, He Y, Wang J, Chen T, Zhong Q, Liang Y, Pierre P, Zou Q, Ye Y, Su B. Li S, et al. Cell Discov. 2024 May 20;10(1):53. doi: 10.1038/s41421-024-00682-z. Cell Discov. 2024. PMID: 38763950 Free PMC article. - A Bcl11bN797K variant isolated from an immunodeficient patient inhibits early thymocyte development in mice.
Matsumoto K, Okuyama K, Sidwell T, Yamashita M, Endo T, Satoh-Takayama N, Ohno H, Morio T, Rothenberg EV, Taniuchi I. Matsumoto K, et al. Front Immunol. 2024 Mar 1;15:1363704. doi: 10.3389/fimmu.2024.1363704. eCollection 2024. Front Immunol. 2024. PMID: 38495886 Free PMC article. - Inactivation of cytidine triphosphate synthase 1 prevents fatal auto-immunity in mice.
Soudais C, Schaus R, Bachelet C, Minet N, Mouasni S, Garcin C, Souza CL, David P, Cousu C, Asnagli H, Parker A, Palmquist-Gomes P, Sepulveda FE, Storck S, Meilhac SM, Fischer A, Martin E, Latour S. Soudais C, et al. Nat Commun. 2024 Mar 4;15(1):1982. doi: 10.1038/s41467-024-45805-y. Nat Commun. 2024. PMID: 38438357 Free PMC article. - Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis.
Savage TM, Fortson KT, de Los Santos-Alexis K, Oliveras-Alsina A, Rouanne M, Rae SS, Gamarra JR, Shayya H, Kornberg A, Cavero R, Li F, Han A, Haeusler RA, Adam J, Schwabe RF, Arpaia N. Savage TM, et al. Immunity. 2024 Feb 13;57(2):303-318.e6. doi: 10.1016/j.immuni.2024.01.009. Epub 2024 Feb 2. Immunity. 2024. PMID: 38309273 - Tracking the role of Aire in immune tolerance to the eye with a TCR transgenic mouse model.
Yin M, Smith JA, Chou M, Chan J, Jittayasothorn Y, Gould DB, Caspi RR, Anderson MS, DeFranco AL. Yin M, et al. Proc Natl Acad Sci U S A. 2024 Jan 30;121(5):e2311487121. doi: 10.1073/pnas.2311487121. Epub 2024 Jan 23. Proc Natl Acad Sci U S A. 2024. PMID: 38261611 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials