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| Status |
Public on Nov 03, 2020 |
| Title |
Critical Regulation of a NDIME/Mef2c Axis in Embryonic Stem Cell Neural Differentiation and Autism |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Recent studies revealed that microdeletion of human chromosome 5q14.3 leads to the occurrence of neurodevelopmental disorders such as autism and intellectual disability, and have identified Mef2c haploinsufficiency as a main cause. Here, we found that a brain-enriched long non-coding RNA, termed NDIME, is located near the Mef2c locus and is required for normal neural differentiation of mouse embryonic stem cells (mESCs). Mechanistic studies showed that exons 1-3 of NDIME interacts with the major component of polycomb repressive complex 2 (PRC2) EZH2, blocking EZH2-mediated trimethylation of histone H3 lysine 27 (H3K27me3) at the Mef2c promoter, ensuring Mef2c transcription. Moreover, both the expression levels of NDIME and Mef2c were significantly downregulated in the hippocampus of autism model mice, while adeno-associated virus (AAV)-mediated expression of NDIME significantly increased the Mef2c expression and ameliorated autism-like behaviors. Collectively, our findings reveal an epigenetic mechanism of NDIME regulating Mef2c transcription and neural differentiation, and the potential effects and application of the NDIME/Mef2c axis in autism.
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| Overall design |
mRNA profiles of wild type (WT), LincNDIME_KO, shCtrl, and shMef2c 46C cells at day 0 and day 5 were generated by deep sequencing.
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| Contributor(s) |
Bai M |
| Citation missing |
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| Submission date |
Jan 14, 2020 |
| Last update date |
Nov 05, 2020 |
| Contact name |
Mingliang Bai |
| E-mail(s) |
727bml@tongji.edu.cn
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| Organization name |
tongji university
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| Street address |
siping road
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| City |
shanghai |
| State/province |
shanghai |
| ZIP/Postal code |
200092 |
| Country |
China |
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| Platforms (1) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA601099 |
| SRA |
SRP241888 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE143606_RAW.tar |
9.1 Mb |
(http)(custom) |
TAR (of TXT) |
| GSE143606_WT-VS-LincNDIME_KO.PossionDis_Method.GeneDiffExpFilter.xls.gz |
332.0 Kb |
(ftp)(http) |
XLS |
| GSE143606_WTandKO_D0_DEGs.xlsx |
63.3 Kb |
(ftp)(http) |
XLSX |
| GSE143606_gene_expression_d0.txt.gz |
540.6 Kb |
(ftp)(http) |
TXT |
| GSE143606_shCtrl-VS-shMef2c.PossionDis_Method.GeneDiffExpFilter.xls.gz |
414.6 Kb |
(ftp)(http) |
XLS |
| GSE143606_shCtrlandshMEF2C_D0_DEGs.xlsx |
17.4 Kb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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