Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 105, Issue 51, Pages 20077-20082Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0806360105
Keywords
cis elements; hindbrain segmentation; Hox genes; regulatory network
Categories
Funding
- Stowers Institute for Medical Research
- Boehringer Ingelheim Funds
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Here, we define a gene regulatory network for Hoxa2, responsible for temporal and spatial expression in hindbrain development. Hoxa2 plays an important role in regulating the regional identity of rhombomere 2 (r2) and is the only Hox gene expressed in this segment. In this study, we found that a Hoxa2 cis-regulatory module consists of five elements that direct expression in r2 of the developing hindbrain. Surprisingly, the module is imbedded in the second coding exon of Hoxa2 and therefore may be constrained by both protein coding and gene regulatory requirements. This highly conserved enhancer consists of two consensus Sox binding sites and several additional elements that act in concert to direct strong r2 specific expression. Our findings provide important insight into the regulation of segmental identity in the anterior hindbrain. Furthermore, they have broader implications in designing arrays and interpreting data from global analyses of gene regulation because regulatory input from coding regions needs to be considered.
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