A global control region defines a chromosomal regulatory landscape containing the HoxD cluster.
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.
Department of Zoology and Animal Biology, NCCR Frontiers in Genetics, University of Geneva, Sciences III, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland.
François
F
Spitz
Federico
F
Gonzalez
Denis
D
Duboule
D024506:5' Flanking Region / Q000235:genetics*; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D033481:Chromosomes, Mammalian / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D020224:Expressed Sequence Tags; D018507:Gene Expression Regulation, Developmental; D005835:Genitalia / Q000196:embryology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D018878:Limb Buds / Q000196:embryology / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D023741:Takifugu / Q000196:embryology
D018398:Homeodomain Proteins; C474231:LNPK protein, human; C474230:Lnpk protein, mouse; D008565:Membrane Proteins