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Article: The ligase PIAS1 restricts natural regulatory T cell differentiation by epigenetic repression

TitleThe ligase PIAS1 restricts natural regulatory T cell differentiation by epigenetic repression
Authors
Liu, BinTahk, SamuelYee, Kathleen M.Fan, GuopingShuai, Ke
Issue Date2010
Citation
Science, 2010, v. 330, n. 6003, p. 521-525 How to Cite?
DOI: http://dx.doi.org/10.1126/science.1193787
AbstractCD4+Foxp3+ regulatory T (Treg) cells are important for maintaining immune tolerance. Understanding the molecular mechanism that regulates Treg differentiation will facilitate the development of effective therapeutic strategies against autoimmune diseases. We report here that the SUMO E3 ligase PIAS1 restricts the differentiation of natural Treg cells by maintaining a repressive chromatin state of the Foxp3 promoter. PIAS1 acts by binding to the Foxp3 promoter to recruit DNA methyltransferases and heterochromatin protein 1 for epigenetic modifications. Pias1 deletion caused promoter demethylation, reduced histone H3 methylation at Lys9, and enhanced promoter accessibility. Consistently, Pias1 -/- mice displayed an increased natural Treg cell population and were resistant to the development of experimental autoimmune encephalomyelitis. Our studies have identified an epigenetic mechanism that negatively regulates the differentiation of natural Treg cells.
Persistent Identifierhttp://hdl.handle.net/10722/365691
ISSN
0036-8075
2023 Impact Factor: 44.7
2023 SCImago Journal Rankings: 11.902

 

DC FieldValueLanguage
dc.contributor.authorLiu, Bin-
dc.contributor.authorTahk, Samuel-
dc.contributor.authorYee, Kathleen M.-
dc.contributor.authorFan, Guoping-
dc.contributor.authorShuai, Ke-
dc.date.accessioned2025-11-05T09:46:52Z-
dc.date.available2025-11-05T09:46:52Z-
dc.date.issued2010-
dc.identifier.citationScience, 2010, v. 330, n. 6003, p. 521-525-
dc.identifier.issn0036-8075-
dc.identifier.urihttp://hdl.handle.net/10722/365691-
dc.description.abstractCD4<sup>+</sup>Foxp3<sup>+</sup> regulatory T (T<inf>reg</inf>) cells are important for maintaining immune tolerance. Understanding the molecular mechanism that regulates T<inf>reg</inf> differentiation will facilitate the development of effective therapeutic strategies against autoimmune diseases. We report here that the SUMO E3 ligase PIAS1 restricts the differentiation of natural T<inf>reg</inf> cells by maintaining a repressive chromatin state of the Foxp3 promoter. PIAS1 acts by binding to the Foxp3 promoter to recruit DNA methyltransferases and heterochromatin protein 1 for epigenetic modifications. Pias1 deletion caused promoter demethylation, reduced histone H3 methylation at Lys<sup>9</sup>, and enhanced promoter accessibility. Consistently, Pias1 <sup>-/-</sup> mice displayed an increased natural T<inf>reg</inf> cell population and were resistant to the development of experimental autoimmune encephalomyelitis. Our studies have identified an epigenetic mechanism that negatively regulates the differentiation of natural T<inf>reg</inf> cells.-
dc.languageeng-
dc.relation.ispartofScience-
dc.titleThe ligase PIAS1 restricts natural regulatory T cell differentiation by epigenetic repression-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1126/science.1193787-
dc.identifier.pmid20966256-
dc.identifier.scopuseid_2-s2.0-77958173509-
dc.identifier.volume330-
dc.identifier.issue6003-
dc.identifier.spage521-
dc.identifier.epage525-
dc.identifier.eissn1095-9203-

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