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Transcriptional activity during NuRD complex induction

ABSTRACT: Molecular functions of the Nucleosome Remodeling and Deacetylation (NuRD) complex in the control of gene expression were investigated using an inducible system to direct its assembly in embryonic stem cells. This dataset profiles time-resolved transcriptional changes in response to NuRD induction.

INSTRUMENT(S): Illumina HiSeq 4000

ORGANISM(S): Mus musculus

SUBMITTER: Paul Bertone

PROVIDER: E-MTAB-6806 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Molecular functions of the Nucleosome Remodeling and Deacetylation (NuRD) complex in the control of gene expression were investigated using an inducible system to direct its assembly in embryonic stem cells. This dataset profiles nascent RNA transcription in response to NuRD induction.

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Project description:Precise control of gene expression plays fundamental roles in brain development, but the roles of chromatin regulators in neuronal connectivity have remained poorly understood. Here, we find that depletion of the nucleosome remodeling and deacetylation (NuRD) complex in the cerebellar cortex by in vivo RNAi in rats and conditional knockout of the core NuRD subunit Chd4 in mice profoundly impairs the establishment of granule neuron parallel fiber/Purkinje cell synapses. In RNA-Seq analyses of Chd4 conditional knockout mice, we identify a set of nearly 200 genes that are repressed by the NuRD complex in the cerebellum in vivo. Genome-wide ChIP-Seq analyses reveal that the NuRD complex selectively decommissions the promoters of NuRD-repressed genes in the cerebellum in vivo by inducing the deacetylation of histone H3K9/14 and H3K27 and demethylation of H3K4 at these genes. Importantly, temporal control of promoter decommissioning and repression of NuRD target genes upon maturation of the cerebellum requires the NuRD complex. Finally, in a targeted in vivo RNAi screen of NuRD-repressed target genes, we identify the transcription factor Nhlh1, the RNA-binding protein Elavl2, and the presynaptic regulator Cplx3 as negative regulators of presynaptic differentiation in the cerebellar cortex. Together, these findings define NuRD-dependent promoter decommissioning as a developmentally regulated programming mechanism that releases the brake on presynaptic differentiation and thereby drives synaptic connectivity in the mammalian brain. Three distinct histone modifications using postnatal day 6 or day 22 cerebella from wild type (WT) or Chd4 conditional knockout (cKO) mice were examined in duplicate using libraries prepared with the Illumina ChIP-Seq DNA Sample Prep Kit and sequenced on the Illumina HiSeq 2000 platform.

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