Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

ChIP-Seq of H3K4 methylation in neurons isolated from E16.5 mouse embryonic cortices from WT and SMCX KO mice

ABSTRACT: We conducted ChIP-Seq of H3K4 methylation in neurons isolated from E16.5 mouse embryonic cortices from WT and SMCX KO mice and harvested after 10 days in vitro culture. We sequenced H3K4me1, H3K4me3 ChIP and Input samples from mouse embryonic cortical neurons cultured in vitro for 10 days. Experiments were performed in biological and technical duplicates.

ORGANISM(S): Mus musculus

SUBMITTER: Saurabh Agarwal

PROVIDER: E-GEOD-61023 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A Mouse Model of X-linked Intellectual Disability Associated with Impaired Removal of Histone Methylation.

Iwase Shigeki S Brookes Emily E Agarwal Saurabh S Badeaux Aimee I AI Ito Hikaru H Vallianatos Christina N CN Tomassy Giulio Srubek GS Kasza Tomas T Lin Grace G Thompson Andrew A Gu Lei L Kwan Kenneth Y KY Chen Chinfei C Sartor Maureen A MA Egan Brian B Xu Jun J Shi Yang Y

Cell reports 20160121 5

Mutations in a number of chromatin modifiers are associated with human neurological disorders. KDM5C, a histone H3 lysine 4 di- and tri-methyl (H3K4me2/3)-specific demethylase, is frequently mutated in X-linked intellectual disability (XLID) patients. Here, we report that disruption of the mouse Kdm5c gene recapitulates adaptive and cognitive abnormalities observed in XLID, including impaired social behavior, memory deficits, and aggression. Kdm5c-knockout brains exhibit abnormal dendritic arbor ...[more]

PMID: 26804915

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Project description:Local translation at the synapse plays key roles in neuron development and activity-dependent synaptic plasticity. mRNAs are translocated from the neuronal soma to the distant synapses as compacted ribonucleoparticles referred to as RNA granules. These contain many RNA-binding proteins, including the Fragile X Mental Retardation Protein (FMRP), the absence of which results in Fragile X Syndrome, the most common inherited form of intellectual disability and the leading genetic cause of autism. Using FMRP as a tracer, we purified a specific population of RNA granules from mouse brain homogenates. Protein composition analyses revealed a strong relationship between polyribosomes and RNA granules. However, the latter have distinct architectural and structural properties, since they are detected as close compact structures as observed by electron microscopy, and converging evidence point to the possibility that these structures emerge from stalled polyribosomes. Time-lapse video microscopy indicated that single granules merge to form cargoes that are transported from the soma to distal locations. Transcriptomic analyses showed that a subset of mRNAs involved in cytoskeleton remodelling and neural development is selectively enriched in RNA granules. One third of the putative mRNA targets described for FMRP appear to be transported in granules and FMRP is more abundant in granules than in polyribosomes. This observation supports a primary role for FMRP in granules biology. Our findings open new avenues for the study of RNA granule dysfunctions in animal models of nervous system disorders, such as Fragile X syndrome. Fragile X syndrome is the most common form of inherited mental retardation affecting approximately 1 female out of 7000 and 1 male out of 4000 worldwide. The syndrome is due to the silencing of a single gene, the Fragile Mental Retardation 1 (FMR1), that codes for the Fragile X mental retardation protein (FMRP). This protein is highly expressed in brain and controls local protein synthesis essential for neuronal development and maturation as well as the formation of neural circuits. Several studies suggest a role for FMRP in the regulation of mRNA transport along axons and dendrites to distant synaptic locations in structures called RNA granules. Here we report the isolation of a particular subpopulation of these structures and the analysis of their architecture and composition in terms of RNA and protein. Also, using time-lapse video microscopy, we monitored granule transport and fusion throughout neuronal processes. These findings open new avenues for the study of RNA transport dysfunctions in animal models of nervous system disorders. The control or reference structure or subcellular fraction are the neuronal polyribosomes while the experimental or test structure or subcellular fraction are the neuronal granules. Three independant replicates were done for each structure. Microarray hybridization was done using a two-color design in full dye-swap.

Dataset Information

ChIP-Seq of H3K4 methylation in neurons isolated from E16.5 mouse embryonic cortices from WT and SMCX KO mice

Publications

A Mouse Model of X-linked Intellectual Disability Associated with Impaired Removal of Histone Methylation.

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