Ferrero Enrico, Fischer Bettina, Russell Steven
Genome Biol. 2014 May 30;15(5):R74. doi: 10.1186/gb-2014-15-5-r74.
Sox proteins encompass an evolutionarily conserved family of transcription factors with critical roles in animal development and stem cell biology. In common with vertebrates, the Drosophila group B proteins SoxNeuro and Dichaete are involved in central nervous system development, where they play both similar and unique roles in gene regulation. Sox genes show extensive functional redundancy across metazoans, but the molecular basis underpinning functional compensation mechanisms at the genomic level are currently unknown.
Using a combination of genome-wide binding analysis and gene expression profiling, we show that SoxNeuro directs embryonic neural development from the early specification of neuroblasts through to the terminal differentiation of neurons and glia. To address the issue of functional redundancy and compensation at a genomic level, we compare SoxNeuro and Dichaete binding, identifying common and independent binding events in wild-type conditions, as well as instances of compensation and loss of binding in mutant backgrounds.
We find that early aspects of group B Sox functions in the central nervous system, such as stem cell maintenance and dorsoventral patterning, are highly conserved. However, in contrast to vertebrates, we find that Drosophila group B1 proteins also play prominent roles during later aspects of neural morphogenesis. Our analysis of the functional relationship between SoxNeuro and Dichaete uncovers evidence for redundant and independent functions for each protein, along with unexpected examples of compensation and interdependency, thus providing new insights into the general issue of transcription factor functional redundancy.
Sox蛋白是一个在进化上保守的转录因子家族,在动物发育和干细胞生物学中发挥着关键作用。与脊椎动物一样,果蝇的B组蛋白SoxNeuro和双胸蛋白参与中枢神经系统发育,它们在基因调控中发挥着相似和独特的作用。Sox基因在多细胞动物中表现出广泛的功能冗余,但目前尚不清楚基因组水平上功能补偿机制的分子基础。
通过结合全基因组结合分析和基因表达谱分析,我们发现SoxNeuro指导胚胎神经发育,从神经母细胞的早期特化一直到神经元和神经胶质细胞的终末分化。为了解决基因组水平上的功能冗余和补偿问题,我们比较了SoxNeuro和双胸蛋白的结合情况,确定了野生型条件下的共同和独立结合事件,以及突变背景下的补偿和结合丧失情况。
我们发现B组Sox蛋白在中枢神经系统中的早期功能,如干细胞维持和背腹模式形成,是高度保守的。然而,与脊椎动物不同的是,我们发现果蝇的B1组蛋白在神经形态发生的后期也发挥着重要作用。我们对SoxNeuro和双胸蛋白功能关系的分析揭示了每种蛋白冗余和独立功能的证据,以及补偿和相互依赖的意外例子,从而为转录因子功能冗余这一普遍问题提供了新的见解。