Prevorovský Martin, Půta Frantisek, Folk Petr
Department of Physiology and Developmental Biology, Faculty of Science, Charles University in Prague, Vinicná 7, Praha 2, Czech Republic.
BMC Genomics. 2007 Jul 13;8:233. doi: 10.1186/1471-2164-8-233.
The CSL (CBF1/RBP-Jkappa/Suppressor of Hairless/LAG-1) transcription factor family members are well-known components of the transmembrane receptor Notch signaling pathway, which plays a critical role in metazoan development. They function as context-dependent activators or repressors of transcription of their responsive genes, the promoters of which harbor the GTG(G/A)GAA consensus elements. Recently, several studies described Notch-independent activities of the CSL proteins.
We have identified putative CSL genes in several fungal species, showing that this family is not confined to metazoans. We have analyzed their sequence conservation and identified the presence of well-defined domains typical of genuine CSL proteins. Furthermore, we have shown that the candidate fungal protein sequences contain highly conserved regions known to be required for sequence-specific DNA binding in their metazoan counterparts. The phylogenetic analysis of the newly identified fungal CSL proteins revealed the existence of two distinct classes, both of which are present in all the species studied.
Our findings support the evolutionary origin of the CSL transcription factor family in the last common ancestor of fungi and metazoans. We hypothesize that the ancestral CSL function involved DNA binding and Notch-independent regulation of transcription and that this function may still be shared, to a certain degree, by the present CSL family members from both fungi and metazoans.
CSL(CBF1/RBP-Jκ/无毛抑制因子/LAG-1)转录因子家族成员是跨膜受体Notch信号通路的知名组成部分,该信号通路在后生动物发育中起关键作用。它们作为其响应基因转录的上下文依赖性激活剂或抑制剂发挥作用,这些基因的启动子含有GTG(G/A)GAA共有元件。最近,多项研究描述了CSL蛋白的Notch非依赖性活性。
我们在几种真菌物种中鉴定出了假定的CSL基因,表明该家族并不局限于后生动物。我们分析了它们的序列保守性,并确定了真正的CSL蛋白典型的明确结构域的存在。此外,我们表明候选真菌蛋白序列包含高度保守的区域,这些区域在其后生动物对应物中是序列特异性DNA结合所必需的。对新鉴定的真菌CSL蛋白的系统发育分析揭示了存在两个不同的类别,这两个类别在所有研究的物种中都存在。
我们的发现支持CSL转录因子家族在真菌和后生动物的最后共同祖先中的进化起源。我们假设祖先的CSL功能涉及DNA结合和Notch非依赖性转录调控,并且这种功能在一定程度上可能仍为来自真菌和后生动物的当前CSL家族成员所共有。