Interactions between LHX3- and ISL1-family LIM-homeodomain transcription factors are conserved in Caenorhabditis elegans

Sci Rep. 2017 Jul 4;7(1):4579. doi: 10.1038/s41598-017-04587-8.

Abstract

LIM-Homeodomain (LIM-HD) transcription factors are highly conserved in animals where they are thought to act in a transcriptional 'LIM code' that specifies cell types, particularly in the central nervous system. In chick and mammals the interaction between two LIM-HD proteins, LHX3 and Islet1 (ISL1), is essential for the development of motor neurons. Using yeast two-hybrid analysis we showed that the Caenorhabditis elegans orthologs of LHX3 and ISL1, CEH-14 and LIM-7 can physically interact. Structural characterisation of a complex comprising the LIM domains from CEH-14 and a LIM-interaction domain from LIM-7 showed that these nematode proteins assemble to form a structure that closely resembles that of their vertebrate counterparts. However, mutagenic analysis across the interface indicates some differences in the mechanisms of binding. We also demonstrate, using fluorescent reporter constructs, that the two C. elegans proteins are co-expressed in a small subset of neurons. These data show that the propensity for LHX3 and Islet proteins to interact is conserved from C. elegans to mammals, raising the possibility that orthologous cell specific LIM-HD-containing transcription factor complexes play similar roles in the development of neuronal cells across diverse species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Animals
  • Binding Sites
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Conserved Sequence
  • Evolution, Molecular
  • Gene Expression Regulation
  • LIM-Homeodomain Proteins / chemistry
  • LIM-Homeodomain Proteins / genetics
  • LIM-Homeodomain Proteins / metabolism*
  • Models, Molecular
  • Multigene Family
  • Multiprotein Complexes
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Domains and Motifs
  • Protein Interaction Mapping
  • Solutions
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • LIM-Homeodomain Proteins
  • Lhx3 protein
  • Multiprotein Complexes
  • Solutions
  • Transcription Factors
  • insulin gene enhancer binding protein Isl-1