Gene Transpositions in the HoxD Complex Reveal a Hierarchy of Regulatory Controls

Cell. 1996 Jun 28;85(7):1025-35. doi: 10.1016/s0092-8674(00)81303-3.

Abstract

Vertebrate Hox genes are activated following a temporal sequence that reflects their linear order in the clusters. We introduced two Hoxd transcription units, labeled with lacZ, to an ectopic 5' position in the HoxD complex. Early expression of the relocated genes was delayed and resembled that of the neighboring Hoxd-13. At later stages, locus-dependent expression in distal limbs and the genital eminence was observed, indicating that common regulatory mechanisms are used for several genes. These experiments also illustrated that neighboring genes can share the same cis-acting sequence and that moving genes around in the complex induces novel regulatory interferences. These results suggest that high order regulation controls the activation of Hox genes and highlight three important constraints responsible for the conservation of Hox gene clustering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA Transposable Elements / genetics*
  • Embryo, Mammalian / physiology
  • Gene Expression Regulation, Developmental / genetics
  • Genetic Complementation Test
  • Genotype
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Phenotype
  • Time Factors
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transgenes / genetics

Substances

  • DNA Transposable Elements
  • Homeodomain Proteins
  • Hoxd11 protein, mouse
  • Transcription Factors