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Histone bivalency regulates the timing of cerebellar granule cell development in vivo [ChIP-seq]

ABSTRACT: Developing neurons undergo a progression of morphological and gene expression changes as they transition from neuronal progenitors to mature, multipolar neurons. Here we use RNA-seq and ChIP-seq to analyze how chromatin modifications control gene expression in a specific type of CNS neuron, the mouse cerebellar granule cell (GC). We find that in proliferating GC progenitors, H3K4me3/H3K27me3 bivalency is common at neuronal genes and undergoes dynamic changes that correlate with gene expression during migration and circuit formation. Inhibiting H3K27 methyltransferases EZH1 and EZH2 in vitro and in organotypic cerebellar slices dramatically altered the expression of bivalent genes and induced the downregulation of migration-related genes and upregulation of synaptic genes, inhibited glial-guided migration and accelerated dendrite formation. These data show that histone bivalency is required to regulate the timing of the progression from progenitor cells to mature neurons.

ORGANISM(S): Mus musculus

PROVIDER: GSE223485 | GEO | 2023/02/06

REPOSITORIES: GEO

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Histone bivalency regulates the timing of cerebellar granule cell development in vivo [RNA-seq]

Project description:Developing neurons undergo a progression of morphological and gene expression changes as they transition from neuronal progenitors to mature, multipolar neurons. Here we use RNA-seq and ChIP-seq to analyze how chromatin modifications control gene expression in a specific type of CNS neuron, the mouse cerebellar granule cell (GC). We find that in proliferating GC progenitors, H3K4me3/H3K27me3 bivalency is common at neuronal genes and undergoes dynamic changes that correlate with gene expression during migration and circuit formation. Inhibiting H3K27 methyltransferases EZH1 and EZH2 in vitro and in organotypic cerebellar slices dramatically altered the expression of bivalent genes and induced the downregulation of migration-related genes and upregulation of synaptic genes, inhibited glial-guided migration and accelerated dendrite formation. These data show that histone bivalency is required to regulate the timing of the progression from progenitor cells to mature neurons.

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