Segmental regulation of Hoxb-3 by kreisler.
Hox genes control regional identity during segmentation of the vertebrate hindbrain into rhombomeres. Here we use transgenic analysis to investigate the upstream mechanisms for regulation of Hoxb-3 in rhombomere(r)5. We identified enhancers from the mouse and chick genes sufficient for r5-restricted expression. Sequence comparisons revealed two blocks of similarity (of 19 and 45 base pairs), which each contain in vitro binding sites for the kreisler protein (Kmrl1), a Maf/b-Zip protein expressed in r5 and r6 (ref. 4). Both sites are required for r5 activity, suggesting that Hoxb-3 is a direct target of kreisler. Multimers of the 19-base-pair (bp) block recreate a Krml1-like pattern in r5/r6, but the 45-bp block mediates expression only in r5. Therefore elements within the 45-bp block restrict the response to Krml1. We identified additional sequences that contain an Ets-related activation site, required for both the activation and restriction to r5. These studies demonstrate that Krml1 directly activates expression of Hoxb-3 in r5 in combination with an Ets-related activation site, and suggest that kreisler plays a primary role in regulating segmental identity through Hox genes.
Manzanares
M
M
Division of Developmental Neurobiology, MRC National Institute for Medical Research, London, UK.
Cordes
S
S
Kwan
C T
CT
Sham
M H
MH
Barsh
G S
GS
Krumlauf
R
R
D000818:Animals; D030161:Avian Proteins; D001665:Binding Sites; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics*; D016350:Leucine Zippers; D051258:MafB Transcription Factor; D051379:Mice; D008822:Mice, Transgenic; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D012249:Rhombencephalon / Q000196:embryology* / Q000378:metabolism; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D029867:Xenopus Proteins
D030161:Avian Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C078105:Hox 2.7 protein, Xenopus; D051258:MafB Transcription Factor; C490406:Mafb protein, mouse; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D029867:Xenopus Proteins; C091157:maf-B protein, chicken