Transcriptomics

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Genome-wide Analysis Reveals Mecp2-dependent Regulation of MicroRNAs in a Mouse Model of Rett Syndrome (high-throughput sequencing)


ABSTRACT: 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. Two pooled total RNA samples (4 pairs of wild-type (WT) and Mecp2-null (KO) male mice; postnatal 6-week, the pre-/early-symptomatic stage) were sequenced in a multiplexed configuration (with distinct barcode sequences). And, six samples (two litters, one WT and two KO male mice in each litter; postnatal 8-week, the symptomatic stage) were sequenced individually.

ORGANISM(S): Mus musculus  

SUBMITTER: Yi Eve Sun   Yi Sun  Hao Wu 

PROVIDER: E-GEOD-24320 | ArrayExpress | 2010-09-29

SECONDARY ACCESSION(S): SRP005132GSE24320PRJNA133481

REPOSITORIES: GEO, ArrayExpress, ENA

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Genome-wide analysis reveals methyl-CpG-binding protein 2-dependent regulation of microRNAs in a mouse model of Rett syndrome.

Wu Hao H   Tao Jifang J   Chen Pauline J PJ   Shahab Atif A   Ge Weihong W   Hart Ronald P RP   Ruan Xiaoan X   Ruan Yijun Y   Sun Yi E YE  

Proceedings of the National Academy of Sciences of the United States of America 20101004 42


MicroRNAs (miRNAs) are a class of small, noncoding RNAs that function as posttranscriptional 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). Although Mecp2 is known to act as a global transcriptional regula  ...[more]

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