| First Author | Sun Y | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 8 | Pages | 4005-13 |
| PubMed ID | 23509362 | Mgi Jnum | J:195294 |
| Mgi Id | MGI:5477864 | Doi | 10.4049/jimmunol.1202911 |
| Citation | Sun Y, et al. (2013) PU.1-Dependent Transcriptional Regulation of miR-142 Contributes to Its Hematopoietic Cell-Specific Expression and Modulation of IL-6. J Immunol 190(8):4005-13 |
| abstractText | MicroRNAs (miRs) have emerged as critical modulators of immune responses, but little is known about their transcriptional regulation and tissue specificity. miR-142 is specifically expressed in hematopoietic tissues and plays an important role in regulating immunity. In this study we identified the key transcriptional elements for regulation of miR-142 and its impact on TLR4-mediated expression of IL-6. The PU.1, C/EBPbeta, and Runx1 transcription factor binding sites are conserved and constitutively occupied by the respective transcription factors in the miR-142 gene promoter only in the hematopoietic cells. Specific knockdown experiments in hematopoietic cells and rescue experiments in nonhematopoietic cells show that PU.1 is critical for miR-142 gene expression and that it synergizes with Runx1, C/EBPbeta, and CBFbeta. Furthermore, TLR4 stimulation enhanced miR-155 whereas experiments with knockdown and mimic expression of miR-155 demonstrated that miR-155 negatively regulates miR-142-3p expression by targeting PU.1. Thus, TLR4 stimulation represses PU.1, resulting in downregulation of miR-142 and increased expression of IL-6. These results collectively reveal the direct cis-acting sequences of miR-142 specific promoter and that transcription factor PU.1 is necessary for its exclusive expression in hematopoietic cells and regulation of IL-6. |
