Abstract
In vitro, mouse embryonic stem (ES) cells can differentiate into many somatic cell types, including neurons and glial cells. When cultured in serum-free medium, ES cells convert spontaneously and efficiently to a neural fate. Previous studies have shown that the neural conversion of mouse ES cells includes both the participation of neural-specific transcription factors and the regulation of epigenetic modifications. However, the intracellular mechanism underlying this intrinsic transition still remains to be further elucidated. Herein, we describe a long intergenic non-coding RNA, LincRNA1230, which participates in the regulation of the neural lineage specification of mouse ES cells. The ectopic forced expression of LincRNA1230 dramatically inhibited mouse ES cells from adopting a neural cell fate, while LincRNA1230 knockdown promoted the conversion of mouse ES cells towards neural progenitors. Mechanistic studies have shown that LincRNA1230 inhibits the activation of early neural genes, such as Pax6 and Sox1, through the modulation of bivalent modifications (tri-methylation of histone3 lysine4 and histone3 lysine27) at the promoters of these genes. The interaction of LincRNA1230 with Wdr5 blocked the localization of Wdr5 at the promoters of early neural genes, thereby inhibiting the enrichment of H3K4me3 modifications at these loci. Collectively, these findings revealed a crucial role for LincRNA1230 in the regulation of the neural differentiation of mouse ES cells.
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Wang, C., Li, G., Wu, Y. et al. LincRNA1230 inhibits the differentiation of mouse ES cells towards neural progenitors. Sci. China Life Sci. 59, 443–454 (2016). https://doi.org/10.1007/s11427-016-5008-7
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DOI: https://doi.org/10.1007/s11427-016-5008-7