Regulation of DNA methylation dictates Cd4 expression during the development of helper and cytotoxic T cell lineages
Huh, Jun R.
Issuree, Priya D.
Green, Michael R.
Littman, Dan R.
UMass Chan AffiliationsDepartment of Molecular, Cell and Cancer Biology
Document TypeJournal Article
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AbstractDuring development, progenitor cells with binary potential give rise to daughter cells that have distinct functions. Heritable epigenetic mechanisms then lock in gene-expression programs that define lineage identity. Regulation of the gene encoding the T cell-specific coreceptor CD4 in helper and cytotoxic T cells exemplifies this process, with enhancer- and silencer-regulated establishment of epigenetic memory for stable gene expression and repression, respectively. Using a genetic screen, we identified the DNA-methylation machinery as essential for maintaining silencing of Cd4 in the cytotoxic lineage. Furthermore, we found a requirement for the proximal enhancer in mediating the removal of DNA-methylation marks from Cd4, which allowed stable expression of Cd4 in helper T cells. Our findings suggest that stage-specific methylation and demethylation events in Cd4 regulate its heritable expression in response to the distinct signals that dictate lineage 'choice' during T cell development.
SourceNat Immunol. 2015 Jul;16(7):746-54. doi: 10.1038/ni.3198. Epub 2015 Jun 1. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/36535
Related ResourcesLink to Article in PubMed