The Transcription factor PU.1 mediates enhancer-promoter looping that is required for IL-1b eRNA and mRNA transcription in mouse myeloma and macrophage cell lines.

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2019
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Abstract
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 non-myeloid lineage, expressed toll-like receptors (TLRs) and activated the transcription factor NF-κB upon stimulation by the bacterial cell wall component lipopolysaccharide (LPS). However, it did not produce cytokines such as IL-1β mRNA. Ectopic PU.1 expression induced remodeling of a novel distal enhancer (located ~10 kbp upstream of the IL-1β 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-κB recruitment and further H3K27 acetylation, both of which were required for enhancer (e)RNA transcription. In murine macrophage RAW246.7 cells, these PU.1-dependent events were constitutively established and readily expressed eRNA and subsequent IL-1β mRNA by LPS stimulation. In summary, this study showed a sequence of epigenetic events in programming IL-1β transcription by the distal enhancer priming and eRNA production mediated by PU.1 and the signal-dependent transcription factor NF-κB.
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Authors Ha, Soon-Duck;Cho, Woohyun;DeKoter, Rodney P;Kim, Sung Ouk;
Journal The Journal of biological chemistry
Year 2019
DOI
jbc.RA119.010149
URL
Keywords
melanoma macrophage gene expression transcription factor erna enhancer pu.1 chromatin modification interleukin 1 (il-1)

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