Project description:Eukaryotic genomes largely consist of non-coding DNA regions. Most non-coding DNA resides in intergenic DNA regions located between a gene and its nearest gene. Here, we demonstrate the relationship between intergenic DNA and gene regulation throughout the mammalian nervous system.
Project description:Eukaryotic genomes largely consist of non-coding DNA regions. Most non-coding DNA resides in intergenic DNA regions located between a gene and its nearest gene. Here, we demonstrate the relationship between intergenic DNA and gene regulation throughout the mammalian nervous system.
Project description:N6-methyladenosine (m6A) affects multiple aspects of mRNA metabolism and regulates developmental transitions by promoting mRNA decay. Little is known about the role of m6A in the adult mammalian nervous system. Here we report that sciatic nerve lesion elevates levels of m6A-tagged transcripts encoding many regeneration-associated genes and protein translation machinery components in the adult mouse dorsal root ganglion (DRG). Single base resolution m6A-CLIP mapping further reveals a dynamic m6A landscape in the adult DRG upon injury. Loss of either m6A methyltransferase complex component Mettl14 or m6A-binding protein Ythdf1 globally attenuates injury induced protein translation in adult DRGs and reduces functional axon regeneration in the peripheral nervous system in vivo. Furthermore, Pten deletion-induced axon regeneration of retinal ganglion neurons in the adult central nervous system is attenuated upon Mettl14 knockdown. Our study reveals a critical epitranscriptomic mechanism in promoting injury-induced protein synthesis and axon regeneration in the adult mammalian nervous system.
Project description:We present evidence for a new level of genome folding, whereby distant domains megabases apart fuse to form meta-domains. Within meta-domains, certain gene promoters pair with structural intergenic elements in the distant TAD. These long-range associations occur in a large fraction of Drosophila neurons, but support transcription in only a subset of cells in the nervous system. Most of the associated genes encode neuronal determinants, including those engaged in axonal guidance and adhesion. We used single cell RNA sequencing (scRNA-seq) to analyze gene misexpression genotypes after deleting intergenic meta-loop anchors.
Project description:Chromatin remodeling factors play important roles in accessibility formation of regulatory DNA. The mechanism by which chromatin remodeling factors regulate regulatory DNA regions that activate expression of cell type-specific genes during the nervous system development remains unknown. Chromatin remodeling complexes have neuron-specific factors, which are often mutated in patients with neurological disease. Here we demonstrate that neuronal chromatin remodeling factors activate neuronal gene expression during the nervous system development.
Project description:We present evidence for a new level of genome folding, whereby distant domains megabases apart fuse to form meta-domains. Within meta-domains, certain gene promoters pair with structural intergenic elements in the distant TAD. These long-range associations occur in a large fraction of Drosophila neurons, but support transcription in only a subset of cells in the nervous system. Most of the associated genes encode neuronal determinants, including those engaged in axonal guidance and adhesion. We used single cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) to identify regions of open chromatin at single cell resolution.