PU.1-Dependent Transcriptional Regulation of miR-142 Contributes to Its Hematopoietic Cell–Specific Expression and Modulation of IL-6

• DOI: 10.4049/jimmunol.1202911
• Publication Date: 2013-03-16T08:26:44Z
• Authors: Yaping Sun; John Sun; Toubai Tomomi; Evelyn Nieves; Nathan Mathewson; Hiroya Tamaki; Rebecca Evers; Pavan Reddy
• Keywords: RUNX1

MicroRNAs (miRs) have emerged as critical modulators of immune responses, but little is known about their transcriptional regulation and tissue specificity. miR-142 specifically expressed in hematopoietic tissues plays an important role regulating immunity. In this study we identified the key elements for its impact on TLR4-mediated expression IL-6. The PU.1, C/EBPβ, Runx1 transcription factor binding sites are conserved constitutively occupied by respective factors gene promoter only cells. Specific knockdown experiments cells rescue nonhematopoietic show that PU.1 it synergizes with Runx1, CBFβ. Furthermore, TLR4 stimulation enhanced miR-155 whereas mimic demonstrated negatively regulates miR-142-3p targeting PU.1. Thus, represses resulting downregulation increased These results collectively reveal direct cis-acting sequences specific necessary exclusive