Carl Sarah H, Russell Steven
Department of Genetics and Cambridge Systems Biology Centre, University of Cambridge, Downing Street, Cambridge, CB2 3EH, UK.
BMC Genomics. 2015 Apr 13;16(1):292. doi: 10.1186/s12864-015-1495-3.
Group B Sox proteins are a highly conserved group of transcription factors that act extensively to coordinate nervous system development in higher metazoans while showing both co-expression and functional redundancy across a broad group of taxa. In Drosophila melanogaster, the two group B Sox proteins Dichaete and SoxNeuro show widespread common binding across the genome. While some instances of functional compensation have been observed in Drosophila, the function of common binding and the extent of its evolutionary conservation is not known.
We used DamID-seq to examine the genome-wide binding patterns of Dichaete and SoxNeuro in four species of Drosophila. Through a quantitative comparison of Dichaete binding, we evaluated the rate of binding site turnover across the genome as well as at specific functional sites. We also examined the presence of Sox motifs within binding intervals and the correlation between sequence conservation and binding conservation. To determine whether common binding between Dichaete and SoxNeuro is conserved, we performed a detailed analysis of the binding patterns of both factors in two species.
We find that, while the regulatory networks driven by Dichaete and SoxNeuro are largely conserved across the drosophilids studied, binding site turnover is widespread and correlated with phylogenetic distance. Nonetheless, binding is preferentially conserved at known cis-regulatory modules and core, independently verified binding sites. We observed the strongest binding conservation at sites that are commonly bound by Dichaete and SoxNeuro, suggesting that these sites are functionally important. Our analysis provides insights into the evolution of group B Sox function, highlighting the specific conservation of shared binding sites and suggesting alternative sources of neofunctionalisation between paralogous family members.
B组Sox蛋白是一组高度保守的转录因子,在高等后生动物中广泛发挥作用以协调神经系统发育,同时在广泛的分类群中表现出共表达和功能冗余。在黑腹果蝇中,两种B组Sox蛋白Dichaete和SoxNeuro在全基因组中显示出广泛的共同结合。虽然在果蝇中已观察到一些功能补偿的实例,但共同结合的功能及其进化保守程度尚不清楚。
我们使用DamID-seq来检查四种果蝇中Dichaete和SoxNeuro的全基因组结合模式。通过对Dichaete结合的定量比较,我们评估了全基因组以及特定功能位点上结合位点的周转率。我们还检查了结合区间内Sox基序的存在以及序列保守性与结合保守性之间的相关性。为了确定Dichaete和SoxNeuro之间的共同结合是否保守,我们对两个物种中这两种因子的结合模式进行了详细分析。
我们发现,虽然由Dichaete和SoxNeuro驱动的调控网络在所研究的果蝇类群中基本保守,但结合位点的周转率很高且与系统发育距离相关。尽管如此,结合在已知的顺式调控模块和核心、经独立验证的结合位点上优先保守。我们在Dichaete和SoxNeuro共同结合的位点观察到最强的结合保守性,表明这些位点在功能上很重要。我们的分析为B组Sox功能的进化提供了见解,突出了共享结合位点的特定保守性,并暗示了旁系同源家族成员之间新功能化的替代来源。