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| Status |
Public on Jun 05, 2015 |
| Title |
The LSD1/KDM1A neuro-specific isoform regulates neuronal differentiation through H3K9 demethylation [Affymetrix] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
During brain development, histone-modifying enzymes play an important role by orchestrating transcriptional programs that regulate neuronal maturation. Lysine-Specific Demethylase 1 (LSD1, also named as KDM1A) functions as a transcriptional repressor by removing methyl groups at lysine 4 of histone H3 (H3K4). In neurons, alternative splicing can include an additional exon (exon E8a) within LSD1 transcripts, generating a LSD1+8a neuro-specific isoform. We here report that LSD1+8a isoform does not have the intrinsic ability to demethylate H3K4. LSD1+8a functions as a co-activator on its target genes by removing H3K9 repressive histone marks. We identify the supervillin protein (SVIL) as a LSD1+8a interacting partner and demonstrate that SVIL protein regulates neuronal maturation by controlling LSD1+8a mediated H3K9 demethylation. Thus, our results show that alternative splicing provides a genius mechanism by which LSD1 isoforms can acquire a dual specificity (H3K9 vs H3K4) and therefore differentially control specific gene expression patterns during brain development.
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| Overall design |
In order to find some LSD1+8a regulated genes at differentiated SH-SY5Y cell lines, we infected SH-SY5Y with control or LSD1+8a shRNA, then induced differentiation with RA and BDNF, (Retinoic acid (RA) (Sigma) was added at a final concentration of 10 μM the next day after plating. After 4 days, the cells were washed three times with PBS and incubated with 50 ng/mL of Brain Derived Neural Factor (BDNF) (Millipore) in serum-free medium for 3 days), we extracted RNA from BDNF induced SH-SY5Y cells for expression analysis.Duplicates were included for Affymetrix Human transcriptome version 2 array.
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| Contributor(s) |
Shi Y, Laurent B, Lv R |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Nov 07, 2014 |
| Last update date |
Oct 29, 2018 |
| Contact name |
Ruitu Lyu |
| E-mail(s) |
lvruitu@gmail.com
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| Organization name |
Institutes of Biomedical Sciences Fudan University
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| Lab |
Epigenetics lab
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| Street address |
138 Yixueyuan Road Xuhui District
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| City |
Shanghai |
| ZIP/Postal code |
200030 |
| Country |
China |
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| Platforms (1) |
| GPL17586 |
[HTA-2_0] Affymetrix Human Transcriptome Array 2.0 [transcript (gene) version] |
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| Samples (4)
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| GSM1541092 |
SH-SY5Y cells with Control shRNA replicate1 |
| GSM1541093 |
SH-SY5Y cells with Control shRNA replicate2 |
| GSM1541094 |
SH-SY5Y cells with LSD1+8a shRNA replicate1 |
| GSM1541095 |
SH-SY5Y cells with LSD1+8a shRNA replicate2 |
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| This SubSeries is part of SuperSeries: |
| GSE63153 |
The LSD1/KDM1A neuro-specific isoform regulates neuronal differentiation through H3K9 demethylation |
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| Relations |
| BioProject |
PRJNA266613 |
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