The lineage-defining factors T-bet and Bcl-6 collaborate to regulate Th1 gene expression patterns
dc.contributor.author | Oestreich, Kenneth J. | en |
dc.contributor.author | Huang, A. C. | en |
dc.contributor.author | Weinmann, A. S. | en |
dc.date.accessioned | 2017-01-09T18:23:54Z | en |
dc.date.available | 2017-01-09T18:23:54Z | en |
dc.date.issued | 2011-05-09 | en |
dc.description.abstract | The T-box transcription factor T-bet is important for the differentiation of naive CD4+ T helper cells (Th cells) into the Th1 phenotype. Much is known about T-bet’s role as a transcriptional activator, but less is known about the mechanisms by which T-bet functionally represses alternative Th cell genetic programs. In this study, we first identify Socs1, Socs3, and Tcf7 (TCF-1) as gene targets that are negatively regulated by T-bet. Significantly, T-bet’s role in the repression of these genes is through a direct interaction with their promoters. Consistent with this, we identified two T-bet DNA-binding elements in the Socs1 promoter that are functionally used to down-regulate transcription in primary Th1 cells. Importantly, T-bet’s novel role in transcriptional repression is because of its ability to physically associate with, and functionally recruit, the transcriptional repressor Bcl-6 to a subset of promoters. Furthermore, T-bet functionally recruits Bcl-6 to the Ifng locus in late stages of Th1 differentiation to repress its activity, possibly to prevent the overproduction of IFN-γ, which could result in autoimmunity. Collectively, these data establish a novel mechanism for T-bet–mediated gene repression in which two lineage-defining transcription factors, one a classical activator and one a repressor, collaborate to promote and properly regulate Th1 development. | en |
dc.description.version | Published version | en |
dc.format.extent | 1001 - 1013 (13) page(s) | en |
dc.format.mimetype | application/pdf | en |
dc.identifier.doi | https://doi.org/10.1084/jem.20102144 | en |
dc.identifier.issn | 0022-1007 | en |
dc.identifier.issue | 5 | en |
dc.identifier.uri | http://hdl.handle.net/10919/74033 | en |
dc.identifier.volume | 208 | en |
dc.language.iso | en | en |
dc.publisher | Rockefeller University Press | en |
dc.relation.uri | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000291425400012&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1 | en |
dc.rights | Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported | en |
dc.rights.holder | The Author(s) | en |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/3.0/ | en |
dc.subject | Immunology | en |
dc.subject | Medicine, Research & Experimental | en |
dc.subject | Research & Experimental Medicine | en |
dc.subject | TRANSCRIPTION FACTOR GATA-3 | en |
dc.subject | INTERFERON-GAMMA | en |
dc.subject | CELL-DIFFERENTIATION | en |
dc.subject | CYTOKINE SIGNALING-1 | en |
dc.subject | TARGET GENES | en |
dc.subject | SUPPRESSOR | en |
dc.subject | COMMITMENT | en |
dc.subject | SOCS-3 | en |
dc.subject | FATE | en |
dc.subject | PLASTICITY | en |
dc.title | The lineage-defining factors T-bet and Bcl-6 collaborate to regulate Th1 gene expression patterns | en |
dc.title.serial | Journal of Experimental Medicine | en |
dc.type | Article - Refereed | en |
dc.type.dcmitype | Text | en |
pubs.organisational-group | /Virginia Tech | en |
pubs.organisational-group | /Virginia Tech/All T&R Faculty | en |
pubs.organisational-group | /Virginia Tech/Faculty of Health Sciences | en |
pubs.organisational-group | /Virginia Tech/University Research Institutes | en |
pubs.organisational-group | /Virginia Tech/University Research Institutes/Virginia Tech Carilion Research Institute | en |
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