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| Status |
Public on Sep 30, 2010 |
| Title |
Genome-wide Analysis Reveals Mecp2-dependent Regulation of MicroRNAs in a Mouse Model of Rett Syndrome (mm8 promoter arrays) |
| Organism |
Mus musculus |
| Experiment type |
Non-coding RNA profiling by genome tiling array
Methylation profiling by genome tiling array
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| Summary |
MicroRNAs (miRNAs) are a class of small non-coding RNAs that function as post-transcriptional regulators of gene expression. Many miRNAs are expressed in the developing brain and regulate multiple aspects of neural development including neurogenesis, dendritogenesis and synapse formation. Rett syndrome (RTT) is a progressive neurodevelopmental disorder caused by mutations in the gene encoding Methyl-CpG binding protein 2 (MECP2). While Mecp2 is known to act as a global transcriptional regulator, miRNAs that are directly regulated by Mecp2 in the brain are not known. Using massively parallel sequencing methods, we have identified miRNAs whose expression is altered in cerebella of Mecp2-null mice before and after the onset of severe neurological symptoms. In vivo genome-wide analyses indicate that promoter regions of a significant fraction of dys-regulated miRNA transcripts, including a large polycistronic cluster of brain-specific miRNAs, are DNA methylated and directly bound by Mecp2. Functional analysis demonstrates that the 3’ untranslated region (UTR) of messenger RNA encoding Brain-derived neurotrophic factor (Bdnf) can be targeted by multiple miRNAs aberrantly up-regulated in absence of Mecp2. Taken together, these results suggest that dys-regulation of miRNAs may contribute to RTT pathoetiology, and also provide a valuable resource to further investigate the role of miRNAs in RTT.
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| Overall design |
Chromatin extracted from postnatal 6-8 week old cerebellar (CB) tissues of wild-type (WT) or Mecp2-null (KO) male mice was immunoprecipitated with indicated antibodies and analyzed by NimbleGen custom mouse 385K promoter tiling microarrays (a 2-array set covering the promoter regions of all Refseq protein-coding genes and miRNA transcripts with predicted transcription start sites). Whole cell extract (WCE) was used as input controls in all experiments. DNA methylation profiles in WT CB were also analyzed by methylated DNA immunoprecipitation (MeDIP) followed by hybridization to the same promoter tiling microarrays (MeDIP-chip).
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| Contributor(s) |
Wu H, Sun Y |
| Citation(s) |
20921386 |
| |
| Submission date |
Sep 22, 2010 |
| Last update date |
Mar 22, 2012 |
| Contact name |
Yi Sun |
| E-mail(s) |
ysun@mednet.ucla.edu
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| Phone |
310-825-9506
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| Organization name |
UCLA
|
| Department |
Molecular and Medical Pharmacology
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| Street address |
635, Charles E. Young Dr. South
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| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
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| Platforms (2) |
| GPL10960 |
NimbleGen mouse 385K Refseq and miRNA promoter tiling, 1 of 2-array set (2007-07-27_MM8_promoters_miRNA) |
| GPL10961 |
NimbleGen mouse 385K Refseq and miRNA promoter tiling, 2 of 2-array set (2007-07-27_MM8_promoters_miRNA) |
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| Samples (8)
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| GSM597225 |
WT CB, Mecp2 ChIP-chip (2/2), exp2 |
| GSM597226 |
KO CB, Mecp2 ChIP-chip (1/2) |
| GSM597227 |
KO CB, Mecp2 ChIP-chip (2/2) |
| GSM597228 |
WT CB, DNA methylation by MeDIP-chip (1/2) |
| GSM597229 |
WT CB, DNA methylation by MeDIP-chip (2/2) |
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| This SubSeries is part of SuperSeries: |
| GSE24329 |
Genome-wide Analysis Reveals Mecp2-dependent Regulation of MicroRNAs in a Mouse Model of Rett Syndrome |
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| Relations |
| BioProject |
PRJNA133723 |
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