Conserved regulatory sequences in Atoh7 mediate non-conserved regulatory responses in retina ontogenesis.
The characterisation of interspecies differences in gene regulation is crucial to understanding the molecular basis of phenotypic diversity and evolution. The atonal homologue Atoh7 participates in the ontogenesis of the vertebrate retina. Our study reveals how evolutionarily conserved, non-coding DNA sequences mediate both the conserved and the species-specific transcriptional features of the Atoh7 gene. In the mouse and chick retina, species-related variations in the chromatin-binding profiles of bHLH transcription factors correlate with distinct features of the Atoh7 promoters and underlie variations in the transcriptional rates of the Atoh7 genes. The different expression kinetics of the Atoh7 genes generate differences in the expression patterns of a set of genes that are regulated by Atoh7 in a dose-dependent manner, including those involved in neurite outgrowth and growth cone migration. In summary, we show how highly conserved regulatory elements are put to use in mediating non-conserved functions and creating interspecies neuronal diversity.
Department of Biochemistry, Sciences II, University of Geneva, 1211 Genève 4, Switzerland. dkrawczyk@ucsd.edu
Dorota
D
Skowronska-Krawczyk
Florence
F
Chiodini
Martin
M
Ebeling
Christine
C
Alliod
Adam
A
Kundzewicz
Diogo
D
Castro
Marc
M
Ballivet
François
F
Guillemot
Lidia
L
Matter-Sadzinski
Jean-Marc
JM
Matter
D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002642:Chick Embryo; D002843:Chromatin / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional; D012160:Retina / Q000196:embryology* / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D002843:Chromatin; D009419:Nerve Tissue Proteins; C117638:Atoh7 protein, mouse; C102938:Neurog2 protein, mouse