Krox20 and kreisler co-operate in the transcriptional control of segmental expression of Hoxb3 in the developing hindbrain

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 tran...

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Bibliographic Details
Published in:The EMBO journal 2002-02, Vol.21 (3), p.365-376
Main Authors: Manzanares, Miguel, Nardelli, Jeannette, Gilardi-Hebenstreit, Pascale, Marshall, Heather, Giudicelli, François, Martínez-Pastor, María Teresa, Krumlauf, Robb, Charnay, Patrick
Format: Article
Language:English
Subjects:
Animals
Avian Proteins
DNA Mutational Analysis
DNA-Binding Proteins - genetics
Early Growth Response Protein 2
EMBO09
EMBO11
Gene Expression Regulation, Developmental
hindbrain
Homeodomain Proteins - genetics
Hox
Hox3 gene
Hox3a gene
Hox3b gene
kreisler
kreisler protein
Krox-20 protein
Krox20
Krox20 protein
MafB Transcription Factor
Mice
Oncogene Proteins
pattern formation
Rhombencephalon - embryology
Rhombencephalon - physiology
Transcription Factors - genetics
Transcriptional Activation
Vertebrates
Xenopus Proteins
Zinc Fingers
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Summary: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.
ISSN:0261-4189
1460-2075
DOI:10.1093/emboj/21.3.365