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| Status |
Public on Jun 05, 2015 |
| Title |
The LSD1/KDM1A neuro-specific isoform regulates neuronal differentiation through H3K9 demethylation [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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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 |
Examination of 2 different LSD1 isoforms LSD1 and LSD1+8a, LSD1+8a's cofactor SVIL, H3K9me2 in SH-SY5Y cells infected with control or LSD1+8a shRNA during neuronal maturation induced with BNDF at Day0(B0) and Day3(B3).ChIP-seq datas were generated by deep sequencer Hiseq2500.
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| Contributor(s) |
Shi Y, Laurent B, Ruitu L |
| Citation missing |
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| Submission date |
Jun 05, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Ruitu Lyu |
| E-mail(s) |
lvruitu@gmail.com
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| Organization name |
Institutes of Biomedical Sciences Fudan University
|
| Lab |
Epigenetics lab
|
| Street address |
138 Yixueyuan Road Xuhui District
|
| City |
Shanghai |
| ZIP/Postal code |
200030 |
| Country |
China |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (23)
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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 |
PRJNA251753 |
| SRA |
SRP042983 |
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