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  • Title: Segmental regulation of Hoxb-3 by kreisler.
    Author: Manzanares M, Cordes S, Kwan CT, Sham MH, Barsh GS, Krumlauf R.
    Journal: Nature; 1997 May 08; 387(6629):191-5. PubMed ID: 9144291.
    Abstract:
    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.
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