| First Author | Xu L | Year | 2010 |
| Journal | Immunity | Volume | 33 |
| Issue | 3 | Pages | 313-25 |
| PubMed ID | 20870174 | Mgi Jnum | J:164648 |
| Mgi Id | MGI:4834927 | Doi | 10.1016/j.immuni.2010.09.001 |
| Citation | Xu L, et al. (2010) Positive and negative transcriptional regulation of the Foxp3 gene is mediated by access and binding of the Smad3 protein to enhancer I. Immunity 33(3):313-25 |
| abstractText | The molecular mechanisms underlying retinoic acid (RA) augmentation of T cell receptor (TCR) and transforming growth factor-beta (TGF-beta)-induced Foxp3 transcription and inhibition of the latter by cytokines such as IL-27 were here shown to be related processes involving modifications of baseline (TGF-beta-induced) phosphorylated Smad3 (pSmad3) binding to a conserved enhancer region (enhancer I). RA augmentation involved the binding of retinoic acid receptor (RAR) and retinoid X receptor (RXR) to a dominant site in enhancer I and a subordinate site in the promoter. This led to increased histone acetylation in the region of the Smad3 binding site and increased binding of pSmad3. Cytokine (IL-27) inhibition involved binding of pStat3 to a gene silencer in a second conserved enhancer region (enhancer II) downstream from enhancer I; this led to loss of pSmad3 binding to enhancer I. Thus, control of accessibility and binding of pSmad3 provides a common framework for positive and negative regulation of TGF-beta-induced Foxp3 transcription. |
