In:
The FEBS Journal, Wiley, Vol. 282, No. 4 ( 2015-02), p. 685-699
Abstract:
Micro RNA s (mi RNA s), a group of noncoding RNA s, function as post‐transcriptional gene regulators and control the establishment, self‐renewal and differentiation of stem cells. Vitamin C has been recognized as a reprogramming enhancer because of its ability to induce a blastocyst‐like state in embryonic stem cells ( ESC s). However, knowledge on the regulation of mi RNA s by vitamin C in ESC s is limited. In this study, we found that vitamin C induced mi RNA expression, particularly of ESC ‐specific mi RNA s. Moreover, vitamin C maintained the mi RNA expression of the Dlk1 – Dio3 imprinting region. The mi RNA s in this region contain identical seed sequences, which target a class of genes, including Kdm6b , Klf13 , and Sox6 , and are mainly related to cell differentiation and development. These genes were significantly downregulated by vitamin C. Notably, miR‐143 promoted self‐renewal of mouse ESC s and suppressed expression of the de novo methyltransferase gene Dnmt3a . Knockdown of miR‐143 by use of its inhibitor counteracted the vitamin C‐induced reduction in Dnmt3a expression, showing that vitamin C repressed Dnmt3a expression via miR‐143. Vitamin C also promoted DNA demethylation, including of pluripotency gene promoters ( Tbx3 , Tcl1 , and Esrrb ) and ESC ‐specific mi RNA promoters (miR‐290–295 and miR‐17–92 clusters), and DNA hydroxymethylation, including of the intergenic differentially methylated region of the Dlk1 – Dio3 region. These results strongly suggested that vitamin C promoted widespread DNA demethylation in gene promoters by modulating epigenetic modifiers, including Dnmt3a , which activated pluripotency genes and ESC ‐specific mi RNA s. Then, differentiation and development genes were repressed by ESC ‐enriched mi RNA s, which maintained the stem cell state.
Type of Medium:
Online Resource
ISSN:
1742-464X
,
1742-4658
DOI:
10.1111/febs.2015.282.issue-4
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2172518-4
SSG:
12
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