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Krox20 hindbrain cis-regulatory landscape: interplay between multiple long-range initiation and autoregulatory
Diane Chomette1, Monique Frain, Silvia Cereghini
1INSERM, U784, Ecole Normale Supérieure, 46 rue d'Ulm, 75230 Paris Cedex 05, France.
Development (Cambridge, England)
|February 24, 2006
Summary
Hindbrain segmentation relies on the Krox20 gene, regulated by three long-range enhancers. These elements initiate and maintain Krox20 expression, crucial for neural development and craniofacial patterning.
Area of Science:
- Developmental Biology
- Neuroscience
- Genetics
Background:
- Vertebrate hindbrain segmentation forms rhombomeres, essential for neuronal organization and craniofacial development.
- The Krox20 gene, a transcription factor, is critical for hindbrain segmentation, controlling segment formation and cell patterning.
Purpose of the Study:
- To investigate the cis-regulatory sequences controlling Krox20 gene expression.
- To elucidate the genetic network governing hindbrain segmentation.
Main Methods:
- Analysis of conserved long-range enhancer elements (A, B, C) regulating Krox20 transcription.
- Mutation analysis of transcription factor binding sites, including vHNF1.
Main Results:
- Three conserved enhancers (A, B, C) control Krox20 expression over long distances (200 kb).
- Elements B and C act as initiators, activated early and independent of Krox20.
- Element B's activity depends on vHNF1, suggesting it directly initiates Krox20 expression in r5.
- Element A establishes a positive autoregulatory loop, maintaining Krox20 expression via Krox20 binding sites.
Conclusions:
- A model for Krox20 expression control in hindbrain and neural crest development is proposed.
- vHNF1 and Krox20 play distinct but coordinated roles in regulating Krox20 transcription via specific enhancers.