Wilanowski Tomasz, Tuckfield Annabel, Cerruti Loretta, O'Connell Sinead, Saint Robert, Parekh Vishwas, Tao Jianning, Cunningham John M, Jane Stephen M
Rotary Bone Marrow Research Laboratory, Royal Melbourne Hospital Research Foundation, c/o Royal Melbourne Hospital Post Office, Grattan Street, Parkville, Victoria 3050, Australia.
Mech Dev. 2002 Jun;114(1-2):37-50. doi: 10.1016/s0925-4773(02)00046-1.
The Drosophila transcription factor Grainyhead regulates several key developmental processes. Three mammalian genes, CP2, LBP-1a and LBP-9 have been previously identified as homologues of grainyhead. We now report the cloning of two new mammalian genes (Mammalian grainyhead (MGR) and Brother-of-MGR (BOM)) and one new Drosophila gene (dCP2) that rewrite the phylogeny of this family. We demonstrate that MGR and BOM are more closely related to grh, whereas CP2, LBP-1a and LBP-9 are descendants of the dCP2 gene. MGR shares the greatest sequence homology with grh, is expressed in tissue-restricted patterns more comparable to grh and binds to and transactivates the promoter of the human Engrailed-1 gene, the mammalian homologue of the key grainyhead target gene, engrailed. This sequence and functional conservation indicates that the new mammalian members of this family play important developmental roles.
果蝇转录因子颗粒头蛋白调控多个关键发育过程。先前已鉴定出三个哺乳动物基因CP2、LBP-1a和LBP-9是颗粒头蛋白的同源物。我们现在报告克隆了两个新的哺乳动物基因(哺乳动物颗粒头蛋白(MGR)和MGR兄弟蛋白(BOM))以及一个新的果蝇基因(dCP2),它们改写了该家族的系统发育。我们证明MGR和BOM与颗粒头蛋白(grh)关系更密切,而CP2、LBP-1a和LBP-9是dCP2基因的后代。MGR与grh具有最大的序列同源性,以更类似于grh的组织限制性模式表达,并结合并激活人类Engrailed-1基因的启动子,Engrailed-1基因是关键颗粒头蛋白靶基因engrailed的哺乳动物同源物。这种序列和功能上的保守性表明该家族新的哺乳动物成员发挥着重要的发育作用。