Segmental regulation of Hoxb-3 by kreisler

Nature. 1997 May 8;387(6629):191-5. doi: 10.1038/387191a0.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Avian Proteins*
  • Binding Sites
  • Chick Embryo
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation, Developmental*
  • Genes, Homeobox*
  • Homeodomain Proteins / genetics*
  • Leucine Zippers
  • MafB Transcription Factor
  • Mice
  • Mice, Transgenic
  • Oncogene Proteins*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-ets
  • Rhombencephalon / embryology*
  • Rhombencephalon / metabolism
  • Sequence Deletion
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Up-Regulation
  • Xenopus Proteins*


  • Avian Proteins
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Hox 2.7 protein, Xenopus
  • MafB Transcription Factor
  • Mafb protein, mouse
  • Oncogene Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • Transcription Factors
  • Xenopus Proteins
  • maf-B protein, chicken