A global control region defines a chromosomal regulatory landscape containing the HoxD cluster

Cell. 2003 May 2;113(3):405-17. doi: 10.1016/s0092-8674(03)00310-6.


During limb development, coordinated expression of several Hoxd genes is required in presumptive digits. We searched for the underlying control sequences upstream from the cluster and found Lunapark (Lnp), a gene which shares limb and CNS expression specificities with both Hoxd genes and Evx2, another gene located nearby. We used a targeted enhancer-trap approach to identify a DNA segment capable of directing reporter gene expression in both digits and CNS, following Lnp, Evx2, and Hoxd-specific patterns. This DNA region showed an unusual interspecies conservation, including with its pufferfish counterpart. It contains a cluster of global enhancers capable of controlling transcription of several genes unrelated in structure or function, thus defining large regulatory domains. These domains were interrupted in the Ulnaless mutation, a balanced inversion that modified the topography of the locus. We discuss the heuristic value of these results in term of locus specific versus gene-specific regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Flanking Region / genetics*
  • Alleles
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chromosomes, Artificial, Bacterial / genetics
  • Chromosomes, Mammalian / genetics*
  • Conserved Sequence / genetics
  • Enhancer Elements, Genetic / genetics*
  • Expressed Sequence Tags
  • Gene Expression Regulation, Developmental*
  • Genitalia / embryology
  • Genitalia / metabolism
  • Homeodomain Proteins / genetics*
  • Humans
  • Limb Buds / embryology
  • Limb Buds / metabolism
  • Membrane Proteins
  • Mice
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Molecular Sequence Data
  • Multigene Family / genetics*
  • Sequence Homology, Nucleic Acid
  • Takifugu / embryology


  • Homeodomain Proteins
  • LNPK protein, human
  • Lnpk protein, mouse
  • Membrane Proteins