Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2007-3-15
pubmed:abstractText
The forkhead family protein FOXP3 acts as a repressor of transcription and is both an essential and sufficient regulator of the development and function of regulatory T cells. The molecular mechanism by which FOXP3-mediated transcriptional repression occurs remains unclear. Here, we report that transcriptional repression by FOXP3 involves a histone acetyltransferase-deacetylase complex that includes histone acetyltransferase TIP60 (Tat-interactive protein, 60 kDa) and class II histone deacetylases HDAC7 and HDAC9. The N-terminal 106-190 aa of FOXP3 are required for TIP60-FOXP3, HDAC7-FOXP3 association, as well as for the transcriptional repression of FOXP3 via its forkhead domain. FOXP3 can be acetylated in primary human regulatory T cells, and TIP60 promotes FOXP3 acetylation in vivo. Overexpression of TIP60 but not its histone acetyltransferase-deficient mutant promotes, whereas knockdown of endogenous TIP60 relieved, FOXP3-mediated transcriptional repression. A minimum FOXP3 ensemble containing native TIP60 and HDAC7 is necessary for IL-2 production regulation in T cells. Moreover, FOXP3 association with HDAC9 is antagonized by T cell stimulation and can be restored by the protein deacetylation inhibitor trichostatin A, indicating a complex dynamic aspect of T suppressor cell regulation. These findings identify a previously uncharacterized complex-based mechanism by which FOXP3 actively mediates transcriptional repression.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-10377430, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-11262386, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-11390982, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-11395403, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-11483607, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-11821859, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-11994312, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-12055628, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-12097365, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-12202037, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-12522256, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-12529406, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-12551922, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-12612578, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-12612581, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-12753745, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-14701752, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-14960713, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-15016909, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-15233782, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-15261457, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-15337792, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-15572685, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-15653507, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-15738302, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-15780990, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-15785757, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-15790681, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-15870014, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-15902688, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-15906405, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-16141325, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-16698308, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-16873067, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-16903909, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-16904321, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-17189186, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-17189187, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-8140620, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-8607265, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-9168977, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-9238046, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-9391053, http://linkedlifedata.com/resource/pubmed/commentcorrection/17360565-9862666
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD4, http://linkedlifedata.com/resource/pubmed/chemical/FOXP3 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Forkhead Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/HDAC7 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/HDAC9 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Histone Acetyltransferases, http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylases, http://linkedlifedata.com/resource/pubmed/chemical/Hydroxamic Acids, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2 Receptor alpha Subunit, http://linkedlifedata.com/resource/pubmed/chemical/KAT5 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins, http://linkedlifedata.com/resource/pubmed/chemical/trichostatin A
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0027-8424
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
104
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4571-6
pubmed:dateRevised
2011-9-28
pubmed:meshHeading
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