A dominant-negative form of mouse SOX2 induces trophectoderm differentiation and progressive polyploidy in mouse embryonic stem cells | |
Li, Jun ; Pan, Guangjin ; Cui, Kai ; Liu, Yuwen ; Xu, Shaobin ; Pei, Duanqing | |
2010-05-11 ; 2010-05-11 | |
关键词 | GENE-EXPRESSION TRANSCRIPTIONAL REGULATION PLURIPOTENCY NANOG OCT4 ENHANCER ANOPHTHALMIA ELEMENTS RENEWAL COMPLEX Biochemistry & Molecular Biology |
中文摘要 | SOX2 plays an important role in early embryogenesis by cooperating with OCT4 in regulating gene expression in fertilized eggs, yet the precise mechanism through which SOX2 accomplishes this important function remains poorly understood. Here, we describe the identification of two nuclear localization signals (NLS) in SOX2 and the generation of a dominant-negative mutant (Dmu-mSox2) by mutating these two NLS in its high mobility group domain. Characterization of this mutant demonstrated that SOX2 shuttles between the cytoplasm and nucleus using these two NLS. The mutant has lost its ability to interact with OCT4, but remains competent to interact with wild-type SOX2. Functionally, Dmu-mSox2 is inactive and unable to cooperate with OCT4 in transactivating target promoters bearing its binding sites. However, Dmu-mSox2 is able to inhibit the activity of wild- type SOX2 and subsequently suppress the activity of downstream genes such as Oct4 and Nanog. When stably expressed in embryonic stem (ES) cells, DmumSox2 triggered progressive doublings of cell ploidy (> 8N), leading to differentiation into the trophectoderm lineage. Knockdown of Sox2 by small interfering RNA also induced trophectoderm differentiation and polyploid formation in mouse ES cells. These results suggest that SOX2 maintains stem cell pluripotency by shuttling between the nucleus and cytoplasm in cooperation with OCT4 to prevent trophectoderm differentiation and polyploid formation in ES cells. |
语种 | 英语 ; 英语 |
出版者 | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC ; BETHESDA ; 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA |
内容类型 | 期刊论文 |
源URL | [http://hdl.handle.net/123456789/27650] |
专题 | 清华大学 |
推荐引用方式 GB/T 7714 | Li, Jun,Pan, Guangjin,Cui, Kai,et al. A dominant-negative form of mouse SOX2 induces trophectoderm differentiation and progressive polyploidy in mouse embryonic stem cells[J],2010, 2010. |
APA | Li, Jun,Pan, Guangjin,Cui, Kai,Liu, Yuwen,Xu, Shaobin,&Pei, Duanqing.(2010).A dominant-negative form of mouse SOX2 induces trophectoderm differentiation and progressive polyploidy in mouse embryonic stem cells.. |
MLA | Li, Jun,et al."A dominant-negative form of mouse SOX2 induces trophectoderm differentiation and progressive polyploidy in mouse embryonic stem cells".(2010). |
个性服务 |
查看访问统计 |
相关权益政策 |
暂无数据 |
收藏/分享 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。
修改评论