| Autor: |
Hossain, Dewan Md Sakib, Panda, Abir K., Manna, Argha, Mohanty, Suchismita, Bhattacharjee, Pushpak, Bhattacharyya, Sankar, Saha, Taniya, Chakraborty, Sreeparna, Kar, Rajiv K., Das, Tanya, Chatterjee, Subhrangsu, Sa, Gaurisankar |
| Rok vydání: |
2013 |
| Předmět: |
|
| Zdroj: |
Immunity. 39(6):1057-1069 |
| ISSN: |
1074-7613 |
| DOI: |
10.1016/j.immuni.2013.11.005 |
| Popis: |
SummaryFoxP3, a lineage-specification factor, executes its multiple activities mostly through transcriptional regulation of target genes. We identified an interleukin-10 (IL-10)-producing FoxP3+ T regulatory cell population that contributes to IL-10-dependent type 2 cytokine bias in breast-cancer patients. Although genetic ablation of FOXP3 inhibited IL10 transcription, genome-wide analysis ruled out its role as a transcription factor for IL10. In-depth analysis revealed that histone acetyl transterase-1, in association with FoxP3, modified the IL10 promoter epigenetically, making a space for docking STAT3-FoxP3 complexes. A predictive docking module with target-receptor specificity, along with exon-deletion and site-directed mutagenesis studies, showed that STAT3 binds through its N-terminal floppy domain to the exon 2 β sheet region of FoxP3 to form STAT3-FoxP3 complexes. Such cotranscriptional activity of FoxP3 extended to other STAT3-target genes that lack FoxP3-binding sites. These results suggest a function of FoxP3, where, failing to achieve direct promoter occupancy, FoxP3 promotes transcription in association with the locus-specific transcription factor STAT3. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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