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Genome-wide maps of chromatin state in medium spiny neurons in the striatum of adult mice

ABSTRACT: Normal brain function critically depends on the interaction between highly specialized neurons that operate within anatomically and functionally distinct brain regions. The fidelity of neuronal specification is contingent upon the robustness of the transcriptional program that supports the neuron type-specific patterns of gene expression. Changes in neuron type-specific gene expression are commonly associated with neurodegenerative disorders including Huntington’s and Alzheimer’s disease. The neuronal specification is driven by gene expression programs that are established during early stages of neuronal development and remain in place in the adult brain. Here we show that the Polycomb repressive complex 2 (PRC2), which supports neuron specification during early differentiation, contributes to the suppression of the transcription program that can be detrimental for the adult neuron function. We show that PRC2 deficiency in adult striatal neurons and in cerebellar Purkinje cells impairs the maintenance of neuron-type specific gene expression. The deficiency in PRC2 has a direct impact on a selected group of genes that is dominated by self-regulating transcription factors normally suppressed in these neurons. The age-dependent progressive transcriptional changes in PRC2-deficient neurons are associated with impaired neuronal function and survival and lead to the development of fatal neurodegenerative disorders in mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE84244 | GEO | 2016/07/29

SECONDARY ACCESSION(S): PRJNA328469

REPOSITORIES: GEO

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Genome-wide maps of chromatin state in medium spiny neurons in the striatum of adult mice

Project description:Normal brain function critically depends on the interaction between highly specialized neurons that operate within anatomically and functionally distinct brain regions. The fidelity of neuronal specification is contingent upon the robustness of the transcriptional program that supports the neuron type-specific patterns of gene expression. Changes in neuron type-specific gene expression are commonly associated with neurodegenerative disorders including Huntingtonâs and Alzheimerâs disease. The neuronal specification is driven by gene expression programs that are established during early stages of neuronal development and remain in place in the adult brain. Here we show that the Polycomb repressive complex 2 (PRC2), which supports neuron specification during early differentiation, contributes to the suppression of the transcription program that can be detrimental for the adult neuron function. We show that PRC2 deficiency in adult striatal neurons and in cerebellar Purkinje cells impairs the maintenance of neuron-type specific gene expression. The deficiency in PRC2 has a direct impact on a selected group of genes that is dominated by self-regulating transcription factors normally suppressed in these neurons. The age-dependent progressive transcriptional changes in PRC2-deficient neurons are associated with impaired neuronal function and survival and lead to the development of fatal neurodegenerative disorders in mice. Medium Spiny neuronal nuclei were isolated from adult mouse striata via NeuN-specific Flourescence Activated Nuclei Sorting.

2016-07-29 | E-GEOD-84244 | biostudies-arrayexpress

Microarray analysis of striatal tissue of wild type and Ezh1/Ezh2 dKO mice at 6 weeks, 3 months, and 6 months

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Next-generation sequencing identifies mRNAs targets that experience significant changes in alternative splicing upon PQBP1 knockdown in mouse embryonic cortical neurons

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