PUBLICATION
A long range distal enhancer controls temporal fine-tuning of PAX6 expression in neuronal precursors
- Authors
- Lacomme, M., Medevielle, F., Bourbon, H.M., Thierion, E., Kleinjan, D.J., Roussat, M., Pituello, F., Bel-Vialar, S.
- ID
- ZDB-PUB-180228-14
- Date
- 2018
- Source
- Developmental Biology 436(2): 94-107 (Journal)
- Registered Authors
- Keywords
- NEUROG2, Neural Tube, PAX6, Retinoic Acid, Transcriptional Regulation
- MeSH Terms
-
- Animals
- Basic Helix-Loop-Helix Transcription Factors/metabolism
- Chick Embryo
- Enhancer Elements, Genetic/genetics*
- Gene Expression Regulation, Developmental
- Immunohistochemistry
- In Situ Hybridization
- Mice
- Nerve Tissue Proteins/metabolism
- Neural Tube/embryology
- Neural Tube/metabolism*
- Neurogenesis/genetics*
- PAX6 Transcription Factor/metabolism*
- Receptors, Retinoic Acid/metabolism
- Signal Transduction/physiology
- Zebrafish
- PubMed
- 29486153 Full text @ Dev. Biol.
Citation
Lacomme, M., Medevielle, F., Bourbon, H.M., Thierion, E., Kleinjan, D.J., Roussat, M., Pituello, F., Bel-Vialar, S. (2018) A long range distal enhancer controls temporal fine-tuning of PAX6 expression in neuronal precursors. Developmental Biology. 436(2):94-107.
Abstract
Proper embryonic development relies on a tight control of spatial and temporal gene expression profiles in a highly regulated manner. One good example is the ON/OFF switching of the transcription factor PAX6 that governs important steps of neurogenesis. In the neural tube PAX6 expression is initiated in neural progenitors through the positive action of retinoic acid signaling and downregulated in neuronal precursors by the bHLH transcription factor NEUROG2. How these two regulatory inputs are integrated at the molecular level to properly fine tune temporal PAX6 expression is not known. In this study we identified and characterized a 940-bp long distal cis-regulatory module (CRM), located far away from the PAX6 transcription unit and which conveys positive input from RA signaling pathway and indirect repressive signal(s) from NEUROG2. These opposing regulatory signals are integrated through HOMZ, a 94bp core region within E940 which is evolutionarily conserved in distant organisms such as the zebrafish. We show that within HOMZ, NEUROG2 and RA exert their opposite temporal activities through a short 60bp region containing a functional RA-responsive element (RARE). We propose a model in which retinoic acid receptors (RARs) and NEUROG2 repressive target(s) compete on the same DNA motif to fine tune temporal PAX6 expression during the course of spinal neurogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping