| First Author | Ha SD | Year | 2019 |
| Journal | J Biol Chem | Volume | 294 |
| Issue | 46 | Pages | 17487-17500 |
| PubMed ID | 31586032 | Mgi Jnum | J:283072 |
| Mgi Id | MGI:6383621 | Doi | 10.1074/jbc.RA119.010149 |
| Citation | Ha SD, et al. (2019) The transcription factor PU.1 mediates enhancer-promoter looping that is required for IL-1beta eRNA and mRNA transcription in mouse melanoma and macrophage cell lines. J Biol Chem 294(46):17487-17500 |
| abstractText | The DNA-binding protein PU.1 is a myeloid lineage-determining and pioneering transcription factor due to its ability to bind "closed" genomic sites and maintain "open" chromatin state for myeloid lineage-specific genes. The precise mechanism of PU.1 in cell type-specific programming is yet to be elucidated. The melanoma cell line B16BL6, although it is nonmyeloid lineage, expressed Toll-like receptors and activated the transcription factor NF-kappaB upon stimulation by the bacterial cell wall component lipopolysaccharide. However, it did not produce cytokines, such as IL-1beta mRNA. Ectopic PU.1 expression induced remodeling of a novel distal enhancer (located approximately 10 kbp upstream of the IL-1beta transcription start site), marked by nucleosome depletion, enhancer-promoter looping, and histone H3 lysine 27 acetylation (H3K27ac). PU.1 induced enhancer-promoter looping and H3K27ac through two distinct PU.1 regions. These PU.1-dependent events were independently required for subsequent signal-dependent and co-dependent events: NF-kappaB recruitment and further H3K27ac, both of which were required for enhancer RNA (eRNA) transcription. In murine macrophage RAW264.7 cells, these PU.1-dependent events were constitutively established and readily expressed eRNA and subsequently IL-1beta mRNA by lipopolysaccharide stimulation. In summary, this study showed a sequence of epigenetic events in programming IL-1beta transcription by the distal enhancer priming and eRNA production mediated by PU.1 and the signal-dependent transcription factor NF-kappaB. |
