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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2010-1-20
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pubmed:abstractText |
Aire induces the expression of a battery of peripheral-tissue self-antigens (PTAs) in thymic stromal cells, promoting the clonal deletion of differentiating T cells that recognize them. Just how Aire targets and induces PTA transcripts remains largely undefined. Screening via Aire-targeted coimmunoprecipitation followed by mass spectrometry, and validating by multiple RNAi-mediated knockdown approaches, we identified a large set of proteins that associate with Aire. They fall into four major functional classes: nuclear transport, chromatin binding/structure, transcription and pre-mRNA processing. One set of Aire interactions centered on DNA protein kinase and a group of proteins it partners with to resolve DNA double-stranded breaks or promote transcriptional elongation. Another set of interactions was focused on the pre-mRNA splicing and maturation machinery, potentially explaining the markedly more effective processing of PTA transcripts in the presence of Aire. These findings suggest a model to explain Aire's widespread targeting and induction of weakly transcribed chromatin regions.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/APECED protein,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Autoantigens,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Topoisomerases, Type II,
http://linkedlifedata.com/resource/pubmed/chemical/DNA topoisomerase II alpha,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Activated Protein Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Prkdc protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1097-4172
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
8
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pubmed:volume |
140
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
123-35
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:20085707-Animals,
pubmed-meshheading:20085707-Antigens, Neoplasm,
pubmed-meshheading:20085707-Autoantigens,
pubmed-meshheading:20085707-Cell Line,
pubmed-meshheading:20085707-DNA Breaks, Double-Stranded,
pubmed-meshheading:20085707-DNA Topoisomerases, Type II,
pubmed-meshheading:20085707-DNA-Activated Protein Kinase,
pubmed-meshheading:20085707-DNA-Binding Proteins,
pubmed-meshheading:20085707-Gene Expression Regulation,
pubmed-meshheading:20085707-Humans,
pubmed-meshheading:20085707-Immune Tolerance,
pubmed-meshheading:20085707-Immunoprecipitation,
pubmed-meshheading:20085707-Mass Spectrometry,
pubmed-meshheading:20085707-Mice,
pubmed-meshheading:20085707-Mice, SCID,
pubmed-meshheading:20085707-Nuclear Proteins,
pubmed-meshheading:20085707-Protein Binding,
pubmed-meshheading:20085707-RNA, Messenger,
pubmed-meshheading:20085707-RNA Processing, Post-Transcriptional,
pubmed-meshheading:20085707-Thymus Gland,
pubmed-meshheading:20085707-Transcription Factors
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pubmed:year |
2010
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pubmed:articleTitle |
Aire's partners in the molecular control of immunological tolerance.
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pubmed:affiliation |
Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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