title: Krox20 and kreisler co-operate in the transcriptional control of segmental expression of Hoxb3 in the developing hindbrain.
abstract: In the segmented vertebrate hindbrain, the Hoxa3 and Hoxb3 genes are expressed at high relative levels in the rhombomeres (r) 5 and 6, and 5, respectively. The single enhancer elements responsible for these activities have been identified previously and shown to constitute direct targets of the transcription factor kreisler, which is expressed in r5 and r6. Here, we have analysed the contribution of the transcription factor Krox20, present in r3 and r5. Genetic analyses demonstrated that Krox20 is required for activity of the Hoxb3 r5 enhancer, but not of the Hoxa3 r5/6 enhancer. Mutational analysis of the Hoxb3 r5 enhancer, together with ectopic expression experiments, revealed that Krox20 binds to the enhancer and synergizes with kreisler to promote Hoxb3 transcription, restricting enhancer activity to their domain of overlap, r5. These analyses also suggested contributions from an Ets-related factor and from putative factors likely to heterodimerize with kreisler. The integration of multiple independent inputs present in overlapping domains by a single enhancer is likely to constitute a general mechanism for the patterning of subterritories during vertebrate development.
authors.affiliation: Division of Developmental Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Miguel
authors.initials: M
authors.lastname: Manzanares
authors.forename: Jeannette
authors.initials: J
authors.lastname: Nardelli
authors.forename: Pascale
authors.initials: P
authors.lastname: Gilardi-Hebenstreit
authors.forename: Heather
authors.initials: H
authors.lastname: Marshall
authors.forename: François
authors.initials: F
authors.lastname: Giudicelli
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Martínez-Pastor
authors.forename: Robb
authors.initials: R
authors.lastname: Krumlauf
authors.forename: Patrick
authors.initials: P
authors.lastname: Charnay
mesh_terms: D000818:Animals; D030161:Avian Proteins; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D051767:Early Growth Response Protein 2; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics*; D051258:MafB Transcription Factor; D051379:Mice; D015513:Oncogene Proteins; D012249:Rhombencephalon / Q000196:embryology / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation; D029867:Xenopus Proteins; D016335:Zinc Fingers
chemical_list: D030161:Avian Proteins; D004268:DNA-Binding Proteins; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D018398:Homeodomain Proteins; C078105:Hox 2.7 protein, Xenopus; C489830:Hoxa2 protein, Xenopus; C080331:Hoxa3 protein, mouse; D051258:MafB Transcription Factor; C490406:Mafb protein, mouse; D015513:Oncogene Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins