Segmental expression of Hoxb-1 is controlled by a highly conserved autoregulatory loop dependent upon exd/pbx.
Comparison of Hoxb-1 regulatory regions from different vertebrates identified three related sequence motifs critical for rhombomere 4 (r4) expression in the hindbrain. Functional analysis in transgenic mice and Drosophila embryos demonstrated that the conserved elements are involved in a positive autoregulatory loop dependent on labial (lab) family members. Binding of Hoxb-1 to these elements in vitro requires cofactors, and the motifs closely resemble the consensus binding site for pbx1, a homolog of the Drosophila extradenticle (exd) homoedomain protein. In vitro exd/pbx serves as a Hoxb-1 cofactor in cooperative binding and in Drosophila expression mediated by the r4 enhancer is dependent on both lab and exd. This provides in vivo and in vitro evidence that r4 expression involves direct autoregulation dependent on cooperative interactions of Hoxb-1 with exd/pbx proteins as cofactors.
Pöpperl
H
H
Medical Research Council, National Institute for Medical Research, London, England.
Bienz
M
M
Studer
M
M
Chan
S K
SK
Aparicio
S
S
Brenner
S
S
Mann
R S
RS
Krumlauf
R
R
D000818:Animals; D001483:Base Sequence; D002645:Chickens; D016384:Consensus Sequence; D017124:Conserved Sequence; D004330:Drosophila / Q000196:embryology / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005399:Fishes; D015870:Gene Expression; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D005810:Multigene Family; D011994:Recombinant Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D015183:Restriction Mapping; D012249:Rhombencephalon / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D014714:Vertebrates
D018398:Homeodomain Proteins; D011994:Recombinant Proteins