Segmental regulation of Hoxb-3 by kreisler

Miguel Manzanares, Sabine Cordes, Chung-Tin Kwan, Mai Har Sham, Greg S. Barsh and Robb Krumlauf
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Miguel Manzanares: MRC National Institute for Medical Research
Sabine Cordes: Beckman Center for Molecular and Genetic Medicine, Stanford University Medical Center
Chung-Tin Kwan: The University of Hong Kong
Mai Har Sham: The University of Hong Kong
Greg S. Barsh: Beckman Center for Molecular and Genetic Medicine, Stanford University Medical Center
Robb Krumlauf: MRC National Institute for Medical Research

Nature, 1997, vol. 387, issue 6629, 191-195

Abstract: Abstract Hox genes control regional identity during segmentation of the vertebrate hindbrain into rhombomeres1–3. Here we use trans-genic analysis to investigate the upstream mechanisms for regulation ofHoxb-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 containin 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 ofkreisler. 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 thatKrml1directly 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.

Date: 1997
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DOI: 10.1038/387191a0

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