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The regulatory T Cell lineage factor Foxp3 regulates gene expression through several distinct mechanisms mostly independent of direct DNA binding
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Xie, Xin, Stubbington, Michael J. T., Nissen, Jesper K., Andersen, Kristian G., Hebenstreit, Daniel, Teichmann, Sarah A. and Betz, Alexander G. (2015) The regulatory T Cell lineage factor Foxp3 regulates gene expression through several distinct mechanisms mostly independent of direct DNA binding. PLoS Genetics, Volume 11 (Number 6). Article number e1005251. doi:10.1371/journal.pgen.1005251 ISSN 1553-7390.
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Official URL: http://dx.doi.org/10.1371/journal.pgen.1005251
Abstract
The lineage factor Foxp3 is essential for the development and maintenance of regulatory T cells, but little is known about the mechanisms involved. Here, we demonstrate that an N-terminal proline-rich interaction region is crucial for Foxp3’s function. Subdomains within this key region link Foxp3 to several independent mechanisms of transcriptional regulation. Our study suggests that Foxp3, even in the absence of its DNA-binding forkhead domain, acts as a bridge between DNA-binding interaction partners and proteins with effector function permitting it to regulate a large number of genes. We show that, in one such mechanism, Foxp3 recruits class I histone deacetylases to the promoters of target genes, counteracting activation-induced histone acetylation and thereby suppressing their expression.
| Item Type: | Journal Article | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Subjects: | Q Science > QR Microbiology | ||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||
| Library of Congress Subject Headings (LCSH): | T cells, Gene expression | ||||||||
| Journal or Publication Title: | PLoS Genetics | ||||||||
| Publisher: | Public Library of Science | ||||||||
| ISSN: | 1553-7390 | ||||||||
| Official Date: | 24 June 2015 | ||||||||
| Dates: |
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| Volume: | Volume 11 | ||||||||
| Number: | Number 6 | ||||||||
| Article Number: | Article number e1005251 | ||||||||
| DOI: | 10.1371/journal.pgen.1005251 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||
| Date of first compliant deposit: | 29 December 2015 | ||||||||
| Date of first compliant Open Access: | 29 December 2015 | ||||||||
| Funder: | Medical Research Council (Great Britain) (MRC), European Research Council (ERC), Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC) | ||||||||
| Grant number: | MC_U105184296 ; ; 260507 ; BB/L006340/1 |
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