Skowronska-Krawczyk Dorota, Chiodini Florence, Ebeling Martin, Alliod Christine, Kundzewicz Adam, Castro Diogo, Ballivet Marc, Guillemot François, Matter-Sadzinski Lidia, Matter Jean-Marc
Department of Biochemistry, Sciences II, University of Geneva, 1211 Genève 4, Switzerland.
Development. 2009 Nov;136(22):3767-77. doi: 10.1242/dev.033449.
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.
基因调控种间差异的表征对于理解表型多样性和进化的分子基础至关重要。无调性同源物Atoh7参与脊椎动物视网膜的个体发生。我们的研究揭示了进化上保守的非编码DNA序列如何介导Atoh7基因的保守和物种特异性转录特征。在小鼠和鸡的视网膜中，bHLH转录因子的染色质结合谱中的物种相关变异与Atoh7启动子的不同特征相关，并构成Atoh7基因转录速率变异的基础。Atoh7基因不同的表达动力学导致一组受Atoh7剂量依赖性调控的基因表达模式产生差异，包括那些参与神经突生长和生长锥迁移的基因。总之，我们展示了高度保守的调控元件如何用于介导非保守功能并创造种间神经元多样性。
