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Omics score: 171

ChIP-sequencing of histone marks in WT and Fmr1-/- (KO) neurons and mice

ABSTRACT: Widespread misregulation of histone modifcations occur in FXS, most notably increases in marks associated with active transcription. Overall design: 7DIV cultured cortical neurons from WT or Fmr1 KO mice were processed for H3K4me3 and H3K27ac ChIP. In addition, neurons sorted from cerebellar tissue from WT and Fmr1 KO BAC-TRAP NeuroD1 P15 mice were used for H3K4me3 ChIP, performed in triplicate

INSTRUMENT(S): Illumina HiSeq 2000 (Mus musculus)

SUBMITTER: Erica Korb

PROVIDER: GSE81911 | GEO | 2017-08-18

SECONDARY ACCESSION(S): PRJNA323399

REPOSITORIES: GEO

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Excess Translation of Epigenetic Regulators Contributes to Fragile X Syndrome and Is Alleviated by Brd4 Inhibition.

Korb Erica E Herre Margaret M Zucker-Scharff Ilana I Gresack Jodi J Allis C David CD Darnell Robert B RB

Cell 20170817 6

Fragile X syndrome (FXS) is a leading genetic cause of intellectual disability and autism. FXS results from the loss of function of fragile X mental retardation protein (FMRP), which represses translation of target transcripts. Most of the well-characterized target transcripts of FMRP are synaptic proteins, yet targeting these proteins has not provided effective treatments. We examined a group of FMRP targets that encode transcriptional regulators, particularly chromatin-associated proteins. Los ...[more]

PMID: 28823556

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Genome-wide analysis identifies aberrant methylation in Fragile X syndrome is specific to the FMR1 locus

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2012-12-13 | E-GEOD-39504 | ArrayExpress

FMR1 targets distinct mRNA sequence elements to regulate protein expression [PAR-CLIP]

Project description:Fragile-X Syndrome (FXS) is a multi-organ disease leading to mental retardation, macro-orchidism in males, and premature ovarian insufficiency in female carriers. FXS is also a prominent monogenic disease associated with autism spectrum disorders (ASD). FXS is typically caused by the loss of FRAGILE X-MENTAL RETARDATION 1 (FMR1) expression, which encodes for the RNA-binding protein (RBP), FMR1 (or FMRP). We report the discovery of the RNA recognition elements (RREs), binding sites, and mRNA targets for wild-type and I304N mutant FMRP isoforms as well as its paralogs, FXR1 and FXR2. RRE frequency, ratio, and distribution determine target mRNA association with FMRP. Among highly-enriched targets, we identified many genes involved in ASD and demonstrate that FMRP can affect their protein levels in cell culture, mice, and human brain. Unexpectedly, we discovered that these targets are also dysregulated in Fmr1-/- mouse ovaries, showing signs of premature follicular overdevelopment. These results indicate that FMRP targets shared signaling pathways across different cellular contexts. As it is become increasingly appreciated that signaling pathways are important to FXS and ASD, our results here provide an invaluable molecular guide towards the pursuit of novel therapeutic targets for these devastating neurological disorders. PAR-CLIP profiling for wild-type and I304N mutant FMRP isoforms as well as paralogs, FXR1 and FXR2.

2012-12-13 | E-GEOD-39682 | ArrayExpress

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