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dc.contributor.authorSellars, MacLean
dc.contributor.authorHuh, Jun R.
dc.contributor.authorDay, Kenneth
dc.contributor.authorIssuree, Priya D.
dc.contributor.authorGalan, Carolina
dc.contributor.authorGobeil, Stephane
dc.contributor.authorAbsher, Devin
dc.contributor.authorGreen, Michael R.
dc.contributor.authorLittman, Dan R.
dc.date2022-08-11T08:09:19.000
dc.date.accessioned2022-08-23T16:26:18Z
dc.date.available2022-08-23T16:26:18Z
dc.date.issued2015-07-01
dc.date.submitted2015-11-30
dc.identifier.citationNat Immunol. 2015 Jul;16(7):746-54. doi: 10.1038/ni.3198. Epub 2015 Jun 1. <a href="http://dx.doi.org/10.1038/ni.3198">Link to article on publisher's site</a>
dc.identifier.issn1529-2908 (Linking)
dc.identifier.doi10.1038/ni.3198
dc.identifier.pmid26030024
dc.identifier.urihttp://hdl.handle.net/20.500.14038/36535
dc.description.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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=26030024&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1038/ni.3198
dc.subjectAnimals
dc.subjectAntigens, CD4
dc.subjectCD4-Positive T-Lymphocytes
dc.subjectCD8-Positive T-Lymphocytes
dc.subjectCell Differentiation
dc.subjectCell Lineage
dc.subjectCells, Cultured
dc.subjectChromatin
dc.subjectDNA (Cytosine-5-)-Methyltransferase
dc.subjectDNA Methylation
dc.subjectFlow Cytometry
dc.subjectGene Expression
dc.subjectHEK293 Cells
dc.subjectHumans
dc.subjectMice, Knockout
dc.subjectMice, Transgenic
dc.subjectRNA Interference
dc.subjectT-Lymphocytes, Cytotoxic
dc.subjectT-Lymphocytes, Helper-Inducer
dc.subjectTranscription Factors
dc.subjectCell Biology
dc.subjectDevelopmental Biology
dc.subjectGenetics
dc.subjectImmunity
dc.subjectMolecular Biology
dc.subjectMolecular Genetics
dc.titleRegulation of DNA methylation dictates Cd4 expression during the development of helper and cytotoxic T cell lineages
dc.typeJournal Article
dc.source.journaltitleNature immunology
dc.source.volume16
dc.source.issue7
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/mccb_pubs/29
dc.identifier.contextkey7884830
html.description.abstract<p>During 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.</p>
dc.identifier.submissionpathmccb_pubs/29
dc.contributor.departmentDepartment of Molecular, Cell and Cancer Biology
dc.source.pages746-54


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