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Critical regulation of a NDIME / MEF 2C axis in embryonic stem cell neural differentiation and autism
Author(s) -
Bai Mingliang,
Ye Dan,
Guo Xudong,
Xi Jiajie,
Liu Nana,
Wu Yukang,
Jia Wenwen,
Wang Guiying,
Chen Wen,
Li Guoping,
Jiapaer Zeyidan,
Kang Jiuhong
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202050283
Subject(s) - translational research , china , research center , translational medicine , translational science , medicine , library science , political science , pathology , computer science , law
A microdeletion within human chromosome 5q14.3 has been associated with the occurrence of neurodevelopmental disorders, such as autism and intellectual disability, and MEF 2C haploinsufficiency was identified as main cause. Here, we report that a brain‐enriched long non‐coding RNA , NDIME , is located near the MEF 2C locus and is required for normal neural differentiation of mouse embryonic stem cells ( mESC s). NDIME interacts with EZH 2, the major component of polycomb repressive complex 2 ( PRC 2), and blocks EZH 2‐mediated trimethylation of histone H3 lysine 27 (H3K27me3) at the Mef2c promoter, promoting MEF 2C transcription. Moreover, the expression levels of both NDIME and MEF 2C were strongly downregulated in the hippocampus of a mouse model of autism, and the adeno‐associated virus ( AAV )‐mediated expression of NDIME in the hippocampus of these mice significantly increased MEF 2C expression and ameliorated autism‐like behaviors. The results of this study reveal an epigenetic mechanism by which NDIME regulates MEF 2C transcription and neural differentiation and suggest potential effects and therapeutic approaches of the NDIME / MEF 2C axis in autism.