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Segmental regulation of Hoxb-3 by kreisler

Author

Listed:
  • Miguel Manzanares

    (MRC National Institute for Medical Research)

  • Sabine Cordes

    (Beckman Center for Molecular and Genetic Medicine, Stanford University Medical Center
    Mount Sinai Hospital)

  • 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)

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.

Suggested Citation

  • Miguel Manzanares & Sabine Cordes & Chung-Tin Kwan & Mai Har Sham & Greg S. Barsh & Robb Krumlauf, 1997. "Segmental regulation of Hoxb-3 by kreisler," Nature, Nature, vol. 387(6629), pages 191-195, May.
    • Handle: RePEc:nat:nature:v:387:y:1997:i:6629:d:10.1038_387191a0
    DOI: 10.1038/387191a0
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