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RSS FeedsThe transcription factor PU.1 mediates enhancer-promoter looping that is required for IL-1{beta} eRNA and mRNA transcription in mouse melanoma and macrophage cell lines [Immunology] (Journal of Biological Chemistry)

 
 

15 november 2019 11:02:53

 
The transcription factor PU.1 mediates enhancer-promoter looping that is required for IL-1{beta} eRNA and mRNA transcription in mouse melanoma and macrophage cell lines [Immunology] (Journal of Biological Chemistry)
 


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-?B upon stimulation by the bacterial cell wall component lipopolysaccharide. However, it did not produce cytokines, such as IL-1? mRNA. Ectopic PU.1 expression induced remodeling of a novel distal enhancer (located ~10 kbp upstream of the IL-1? 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-?B 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-1? mRNA by lipopolysaccharide stimulation. In description, this study showed a sequence of epigenetic events in programming IL-1? transcription by the distal enhancer priming and eRNA production mediated by PU.1 and the signal-dependent transcription factor NF-?B.


 
194 viewsCategory: Biochemistry
 
A thiazole-derived oridonin analogue exhibits antitumor activity by directly and allosterically inhibiting STAT3 [Gene Regulation] (Journal of Biological Chemistry)
Xenogeneic modulation of the ClpCP protease of Bacillus subtilis by a phage-encoded adaptor-like protein [Protein Synthesis and Degradation] (Journal of Biological Chemistry)
 
 
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