Regulation of the pluripotency marker Rex-1 by Nanog and Sox2.
نویسندگان
چکیده
Rex-1 (Zfp-42) is a known marker for undifferentiated embryonic stem cells and teratocarcinoma cells. However, the mechanism by which Rex-1 is regulated in pluripotent cells remains unresolved. Here we report that Nanog, an Nk-2 homeodomain protein known for its role in maintaining stem cell pluripotency, is a transcription activator for the Rex-1 promoter. Knockdown of Nanog in embryonic stem cells resulted in a reduction of Rex-1 expression, whereas forced expression of Nanog in P19 stimulated Rex-1 expression. Employing a Rex-1 reporter, we demonstrate that Nanog transactivates Rex-1 directly. Serial deletion studies mapped the Nanog-responsive element between -187 and -286 of the Rex-1 promoter. Although Oct-3/4 and Sox2 can both transactivate Rex-1 promoter, only Sox2 cooperates with Nanog in up-regulating Rex-1. Furthermore, we demonstrate that the C terminus of Nanog is responsible for transactivating the Rex-1 promoter, a function that can be substituted for by a viral transactivator Vp16 efficiently in NIH3T3 cells but less so in P19 cells. Taking these findings together, we conclude that Rex-1 is a direct target of Nanog, which is augmented by Sox2 and Oct-3/4.
منابع مشابه
P-106: Comparative Expression of The Stemness Gene Oct-4, Nanog, Sox-2 and Rex-1 in Normal Endometrium and in Endometriosis
Background Endometriosis is a gynecological disease defined as the presence of endometrial tissue outside the uterine cavity, which caused by various factors. Recent evidences support the presence of endometrial stem cells and their possible involvement in endometriosis. Related studies mainly focus on stemness-related genes, and pluripotency markers may play a role in the etiology of endometri...
متن کاملP-67: Quantitative Expression of Pluripotency Specific-Genes in Mouse Blastocysts Produced by In Vitro Fertilization
Background: The efficiency of in vitro fertilization (IVF) is still low to be developed to blastocyst stage probably because of environmental conditions. It is likely that in vitro environment can not exactly mimic in vivo environment due to differences in media, metabolic content, atmospheric composition, temperature and pH. Therefore it may affect embryo quality by changing in embryo gene exp...
متن کاملZic3 is required for maintenance of pluripotency in embryonic stem cells.
Embryonic stem (ES) cell pluripotency is dependent upon sustained expression of the key transcriptional regulators Oct4, Nanog, and Sox2. Dissection of the regulatory networks downstream of these transcription factors has provided critical insight into the molecular mechanisms that regulate ES cell pluripotency and early differentiation. Here we describe a role for Zic3, a member of the Gli fam...
متن کاملAnalysis of pluripotency marker expression in human glioblastoma multiforme cells treated with conditioned medium
Glioblastoma multiforme (GBM) is the most aggressive form of Background malignant glioma and is also known as grade IV astrocytoma. This might be due to the presence of cancer stem cells with high pluripotency and ability of self-renewal. Recently, it has been reported that tumor stroma cells, including mesencyhmal stem cells (MSCs), secrete factors that affect cancer cell growth. Until now, th...
متن کاملOrphan nuclear receptor GCNF is required for the repression of pluripotency genes during retinoic acid-induced embryonic stem cell differentiation.
Embryonic stem (ES) cell pluripotency and differentiation are controlled by a network of transcription factors and signaling molecules. Transcription factors such as Oct4 and Nanog are required for self-renewal and maintain the undifferentiated state of ES cells. Decreases in the expression of these factors indicate the initiation of differentiation of ES cells. Inactivation of the gene encodin...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Journal of biological chemistry
دوره 281 33 شماره
صفحات -
تاریخ انتشار 2006