LncRNA lncLy6C induced by microbiota metabolite butyrate promotes differentiation of Ly6C high to Ly6C int/neg macrophages through lncLy6C/C/EBPβ/Nr4A1 axis
Macrophages are mainly divided into two populations, which play a different role in physiological and pathological conditions. The differentiation of these cells may be regulated by transcription factors. However, it is unclear how to modulate these transcription factors to affect differentiation of...
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Published in | Cell discovery Vol. 6; no. 1; p. 87 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
24.11.2020
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Online Access | Get full text |
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Summary: | Macrophages are mainly divided into two populations, which play a different role in physiological and pathological conditions. The differentiation of these cells may be regulated by transcription factors. However, it is unclear how to modulate these transcription factors to affect differentiation of these cells. Here, we found that lncLy6C, a novel ultraconserved lncRNA, promotes differentiation of Ly6C
inflammatory monocytes into Ly6C
resident macrophages. We demonstrate that gut microbiota metabolites butyrate upregulates the expression of lncLy6C. LncLy6C deficient mice had markedly increased Ly6C
pro-inflammatory monocytes and reduced Ly6C
resident macrophages. LncLy6C not only bound with transcription factor C/EBPβ but also bound with multiple lysine methyltransferases of H3K4me3 to specifically promote the enrichment of C/EBPβ and H3K4me3 marks on the promoter region of Nr4A1, which can promote Ly6C
into Ly6C
macrophages. As a result, lncLy6C causes the upregulation of Nr4A1 to promote Ly6C
inflammatory monocytes to differentiate into Ly6C
resident macrophages. |
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ISSN: | 2056-5968 2056-5968 |