title: Replication-coupled chromatin assembly generates a neuronal bilateral asymmetry in C. elegans.
abstract: Although replication-coupled chromatin assembly is known to be important for the maintenance of patterns of gene expression through sequential cell divisions, the role of replication-coupled chromatin assembly in controlling cell differentiation during animal development remains largely unexplored. Here we report that the CAF-1 protein complex, an evolutionarily conserved histone chaperone that deposits histone H3-H4 proteins onto replicating DNA, is required to generate a bilateral asymmetry in the C. elegans nervous system. A mutation in 1 of 24 C. elegans histone H3 genes specifically eliminates this aspect of neuronal asymmetry by causing a defect in the formation of a histone H3-H4 tetramer and the consequent inhibition of CAF-1-mediated nucleosome formation. Our results reveal that replication-coupled nucleosome assembly is necessary to generate a bilateral asymmetry in C. elegans neuroanatomy and suggest that left-right asymmetric epigenetic regulation can establish bilateral asymmetry in the nervous system.
authors.affiliation: Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Shunji
authors.initials: S
authors.lastname: Nakano
authors.forename: Bruce
authors.initials: B
authors.lastname: Stillman
authors.forename: H Robert
authors.initials: HR
authors.lastname: Horvitz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D004261:DNA Replication; D057890:Epigenomics; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D009420:Nervous System / Q000196:embryology; D009474:Neurons / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D029742:Caenorhabditis elegans Proteins; D006657:Histones; D009707:Nucleosomes; C505139:ccf-1 protein, C elegans