Promoter Decommissioning by the NuRD Chromatin Remodeling Complex Triggers Synaptic Connectivity in the Mammalian Brain
Author
Yamada, Tomoko
Cho, Ha Young
Murphy, J. Patrick
Fioravante, Diasynou
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1016/j.neuron.2014.05.039Metadata
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Yamada, Tomoko, Yue Yang, Martin Hemberg, Toshimi Yoshida, Ha Young Cho, J. Patrick Murphy, Diasynou Fioravante, et al. 2014. Promoter Decommissioning by the NuRD Chromatin Remodeling Complex Triggers Synaptic Connectivity in the Mammalian Brain. Neuron 83, no. 1: 122–134. doi:10.1016/j.neuron.2014.05.039.Abstract
Precise control of gene expression plays fundamental roles in brain development, but the roles of chromatin regulators in neuronal connectivity have remained poorly understood. We report that depletion of the NuRD complex by in vivo RNAi and conditional knockout of the core NuRD subunit Chd4 profoundly impairs the establishment of granule neuron parallel fiber/Purkinje cell synapses in the rodent cerebellar cortex in vivo. By interfacing genome-wide sequencing of transcripts and ChIP-seq analyses, we uncover a network of repressed genes and distinct histone modifications at target gene promoters that are developmentally regulated by the NuRD complex in the cerebellum in vivo. Finally, in a targeted in vivo RNAi screen of NuRD target genes, we identify a program of NuRD-repressed genes that operate as critical regulators of presynaptic differentiation in the cerebellar cortex. Our findings define NuRD-dependent promoter decommissioning as a developmentally regulated programming mechanism that drives synaptic connectivity in the mammalian brain.Other Sources
http://www.ncbi.nlm.nih.gov/pubmed/24991957Terms of Use
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