Identification of cis-regulatory elements from the C. elegans Hox gene lin-39 required for embryonic expression and for regulation by the transcription factors LIN-1, LIN-31 and LIN-39

Dev Biol. 2006 Sep 15;297(2):550-65. doi: 10.1016/j.ydbio.2006.05.008. Epub 2006 May 19.


Expression of the Caenorhabditis elegans Hox gene lin-39 begins in the embryo and continues in multiple larval cells, including the P cell lineages that generate ventral cord neurons (VCNs) and vulval precursor cells (VPCs). lin-39 is regulated by several factors and by Wnt and Ras signaling pathways; however, no cis-acting sites mediating lin-39 regulation have been identified. Here, we describe three elements controlling lin-39 expression: a 338-bp upstream fragment that directs embryonic expression in P5-P8 and their descendants in the larva, a 247-bp intronic region sufficient for VCN expression, and a 1.3-kb upstream cis-regulatory module that drives expression in the VPC P6.p in a Ras-dependent manner. Three trans-acting factors regulate expression via the 1.3-kb element. A single binding site for the ETS factor LIN-1 mediates repression in VPCs other than P6.p; however, loss of LIN-1 decreases expression in P6.p. Therefore, LIN-1 acts both negatively and positively on lin-39 in different VPCs. The Forkhead domain protein LIN-31 also acts positively on lin-39 in P6.p via this module. Finally, LIN-39 itself binds to this element, suggesting that LIN-39 autoregulates its expression in P6.p. Therefore, we have begun to unravel the cis-acting sites regulating lin-39 Hox gene expression and have shown that lin-39 is a direct target of the Ras pathway acting via LIN-1 and LIN-31.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / physiology*
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation, Developmental*
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Homeodomain Proteins / physiology
  • Molecular Sequence Data
  • Neurons / metabolism
  • Protein Structure, Tertiary
  • Sequence Homology, Nucleic Acid
  • Transcription Factors / physiology*


  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Lin-1 protein, C elegans
  • Transcription Factors
  • lin-31 protein, C elegans
  • lin-39 protein, C elegans