LncRNA lncLy6C induced by microbiota metabolite butyrate promotes differentiation of Ly6Chigh to Ly6Cint/neg macrophages through lncLy6C/C/EBPβ/Nr4A1 axis
Abstract 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 different...
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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 |
London
Springer Nature B.V
24.11.2020
Springer Singapore |
Subjects | |
Online Access | Get full text |
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Summary: | Abstract
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
high
inflammatory monocytes into Ly6C
low/neg
resident macrophages. We demonstrate that gut microbiota metabolites butyrate upregulates the expression of
lncLy6C
.
LncLy6C
deficient mice had markedly increased Ly6C
high
pro-inflammatory monocytes and reduced Ly6C
neg
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
high
into Ly6C
neg
macrophages. As a result,
lncLy6C
causes the upregulation of Nr4A1 to promote Ly6C
high
inflammatory monocytes to differentiate into Ly6C
int/neg
resident macrophages. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2056-5968 2056-5968 |
DOI: | 10.1038/s41421-020-00211-8 |