title: LincRNA1230 inhibits the differentiation of mouse ES cells towards neural progenitors.
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.
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Science and Technology, Tongji University, Shanghai, 200092, China.
authors.forename: Chenxin
authors.initials: C
authors.lastname: Wang
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Science and Technology, Tongji University, Shanghai, 200092, China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Li
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Science and Technology, Tongji University, Shanghai, 200092, China.
authors.forename: Yukang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Science and Technology, Tongji University, Shanghai, 200092, China.
authors.forename: Jiajie
authors.initials: J
authors.lastname: Xi
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Science and Technology, Tongji University, Shanghai, 200092, China. jhkang@tongji.edu.cn.
authors.forename: Jiuhong
authors.initials: J
authors.lastname: Kang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D016895:Culture Media, Serum-Free; D053595:Embryonic Stem Cells / Q000166:cytology*; D005786:Gene Expression Regulation; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology*; D011506:Proteins / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism
chemical_list: D016895:Culture Media, Serum-Free; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D062085:RNA, Long Noncoding; C443118:Wdr5 protein, mouse
keywords: Wdr5; bivalent modification; long non-coding RNA (lncRNA); mouse ES cells; neural differentiation