Replication-coupled chromatin assembly generates a neuronal bilateral asymmetry in C. elegans

Cell. 2011 Dec 23;147(7):1525-36. doi: 10.1016/j.cell.2011.11.053. Epub 2011 Dec 15.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Body Patterning
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / metabolism
  • Chromatin Assembly and Disassembly*
  • DNA Replication*
  • Epigenomics*
  • Histones / chemistry
  • Histones / metabolism
  • Molecular Sequence Data
  • Nervous System / embryology
  • Neurons / metabolism
  • Nucleosomes / metabolism
  • Sequence Alignment

Substances

  • Caenorhabditis elegans Proteins
  • Histones
  • Nucleosomes
  • ccf-1 protein, C elegans