Histone methylation restrains the expression of subtype-specific genes during terminal neuronal differentiation in Caenorhabditis elegans

PLoS Genet. 2013;9(12):e1004017. doi: 10.1371/journal.pgen.1004017. Epub 2013 Dec 12.

Abstract

Although epigenetic control of stem cell fate choice is well established, little is known about epigenetic regulation of terminal neuronal differentiation. We found that some differences among the subtypes of Caenorhabditis elegans VC neurons, particularly the expression of the transcription factor gene unc-4, require histone modification, most likely H3K9 methylation. An EGF signal from the vulva alleviated the epigenetic repression of unc-4 in vulval VC neurons but not the more distant nonvulval VC cells, which kept unc-4 silenced. Loss of the H3K9 methyltransferase MET-2 or H3K9me2/3 binding proteins HPL-2 and LIN-61 or a novel chromodomain protein CEC-3 caused ectopic unc-4 expression in all VC neurons. Downstream of the EGF signaling in vulval VC neurons, the transcription factor LIN-11 and histone demethylases removed the suppressive histone marks and derepressed unc-4. Behaviorally, expression of UNC-4 in all the VC neurons caused an imbalance in the egg-laying circuit. Thus, epigenetic mechanisms help establish subtype-specific gene expression, which are needed for optimal activity of a neural circuit.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development*
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Differentiation / genetics*
  • Epigenesis, Genetic / genetics
  • Female
  • Gene Expression Regulation, Developmental
  • Histones / genetics*
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Methylation
  • Neurons / cytology*
  • Neurons / physiology
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Signal Transduction / genetics
  • Vulva / growth & development

Substances

  • Caenorhabditis elegans Proteins
  • Histones
  • Homeodomain Proteins
  • Nuclear Proteins
  • unc-4 protein, C elegans