Identification and functional characterization of a primate-specific E2F1 binding motif regulating MCPH1 expression
文献类型：期刊论文
| 作者 | Shi L1,2; Su B[*]1 |
| 刊名 | FEBS JOURNAL
 |
| 出版日期 | 2012 |
| 卷号 | 279期号:3页码:491-503 |
| 关键词 | E2F1 evolution gene regulation MCPH1 primates promoter activity |
| 通讯作者 | sub@mail.kiz.ac.cn |
| 合作状况 | 其它 |
| 英文摘要 | MCPH1 (also named BRIT1) is one of the known genes responsible for autosomal recessive primary microcephaly (small head syndrome), suggesting its important role in brain development. The interaction of MCPH1 with transcriptional factors like E2F1 is required for the activation of cell cycle checkpoint, DNA repair and apoptosis. However, the molecular mechanism of MCPH1 regulation is currently unclear. Here, we cloned the human MCPH1 promoter and we identified a novel E2F1 binding motif located in the proximal promoter region of MCPH1. The experiments using electrophoretic mobility shift and promoter assays showed that E2F1 could stimulate MCPH1 transcription by direct binding to the E2F1 motif. Overexpression of E2F1 led to the upregulation of MCPH1 transcription, and knocking down the endogenous E2F1 resulted in the inhibition of the MCPH1 promoter activity. Surprisingly, sequence comparison of vertebrate species suggested that the identified E2F1 binding motif is primate specific, consistent with the previous observation of rapid evolution of MCPH1 protein sequence in primates. We propose that during primate evolution MCPH1 has acquired a novel E2F1 binding motif in its promoter which may act as a parallel mechanism, acting together with the rapid protein sequence changes in primates, and eventually contributed to brain enlargement during primate evolution and human origin. |
| 收录类别 | SCI |
| 资助信息 | This work was supported by grants from the National 973 Project of China (grant number 2011CBA00401), the National Natural Science Foundation of China (grant numbers 31130051 and 31071101) and the Natural Science Foundation of Yunnan Province of China (grant numbers 2007C100M and 2009CD107). |
| 语种 | 英语 |
| WOS记录号 | WOS:000299255500011 |
| 公开日期 | 2012-03-20 |
| 源URL | [http://159.226.149.42:8088/handle/353002/6881]  |
| 专题 | 昆明动物研究所_比较基因组学 昆明动物研究所_遗传资源与进化国家重点实验室 |
| 作者单位 | 1.State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences China 2.Graduate School of Chinese Academy of Sciences, Beijing, China |
| 推荐引用方式 GB/T 7714 | Shi L,Su B[*]. Identification and functional characterization of a primate-specific E2F1 binding motif regulating MCPH1 expression[J]. FEBS JOURNAL,2012,279(3):491-503. |
| APA | Shi L,&Su B[*].(2012).Identification and functional characterization of a primate-specific E2F1 binding motif regulating MCPH1 expression.FEBS JOURNAL,279(3),491-503. |
| MLA | Shi L,et al."Identification and functional characterization of a primate-specific E2F1 binding motif regulating MCPH1 expression".FEBS JOURNAL 279.3(2012):491-503. |
入库方式： OAI收割
来源：昆明动物研究所
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