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    Cdc6 expression represses E-cadherin transcription and activates adjacent replication origins

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    Author
    Sideridou, Maria; Zakopoulou, Roubini; Evangelou, Konstantinos; Liontos, Michalis; Kotsinas, Athanassios; Rampakakis, Emmanouil; Gagos, Sarantis; Kahata, Kaoru; Grabusic, Kristina; Gkouskou, Kalliopi; Trougakos, Ioannis P.; Kolettas, Evangelos; Georgakilas, Alexandros G.; Volarevic, Sinisa; Eliopoulos, Aristides G.; Zannis-Hadjopoulos, Maria; Moustakas, Aristidis; Gorgoulis, Vassilis G.
    Abstract
    E-cadherin (CDH1) loss occurs frequently in carcinogenesis, contributing to invasion and metastasis. We observed that mouse and human epithelial cell lines overexpressing the replication licensing factor Cdc6 underwent phenotypic changes with mesenchymal features and loss of E-cadherin. Analysis in various types of human cancer revealed a strong correlation between increased Cdc6 expression and reduced E-cadherin levels. Prompted by these findings, we discovered that Cdc6 repressed CDH1 transcription by binding to the E-boxes of its promoter, leading to dissociation of the chromosomal insulator CTCF, displacement of the histone variant H2A.Z, and promoter heterochromatinization. Mutational analysis identified the Walker B motif and C-terminal region of Cdc6 as essential for CDH1 transcriptional suppression. Strikingly, CTCF displacement resulted in activation of adjacent origins of replication. These data demonstrate that Cdc6 acts as a molecular switch at the E-cadherin locus, linking transcriptional repression to activation of replication, and provide a telling example of how replication licensing factors could usurp alternative programs to fulfill distinct cellular functions.
    URI
    http://hdl.handle.net/10342/5447
    Date
    2011-12
    Citation:
    APA:
    Sideridou, Maria, & Zakopoulou, Roubini, & Evangelou, Konstantinos, & Liontos, Michalis, & Kotsinas, Athanassios, & Rampakakis, Emmanouil, & Gagos, Sarantis, & Kahata, Kaoru, & Grabusic, Kristina, & Gkouskou, Kalliopi, & Trougakos, Ioannis P., & Kolettas, Evangelos, & Georgakilas, Alexandros G., & Volarevic, Sinisa, & Eliopoulos, Aristides G., & Zannis-Hadjopoulos, Maria, & Moustakas, Aristidis, & Gorgoulis, Vassilis G.. (December 2011). Cdc6 expression represses E-cadherin transcription and activates adjacent replication origins. The Journal of Cell Biology, (195:7), p.1123-1140. Retrieved from http://hdl.handle.net/10342/5447

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    MLA:
    Sideridou, Maria, and Zakopoulou, Roubini, and Evangelou, Konstantinos, and Liontos, Michalis, and Kotsinas, Athanassios, and Rampakakis, Emmanouil, and Gagos, Sarantis, and Kahata, Kaoru, and Grabusic, Kristina, and Gkouskou, Kalliopi, and Trougakos, Ioannis P., and Kolettas, Evangelos, and Georgakilas, Alexandros G., and Volarevic, Sinisa, and Eliopoulos, Aristides G., and Zannis-Hadjopoulos, Maria, and Moustakas, Aristidis, and Gorgoulis, Vassilis G.. "Cdc6 expression represses E-cadherin transcription and activates adjacent replication origins". The Journal of Cell Biology. 195:7. (1123-1140.), December 2011. February 26, 2021. http://hdl.handle.net/10342/5447.
    Chicago:
    Sideridou, Maria and Zakopoulou, Roubini and Evangelou, Konstantinos and Liontos, Michalis and Kotsinas, Athanassios and Rampakakis, Emmanouil and Gagos, Sarantis and Kahata, Kaoru and Grabusic, Kristina and Gkouskou, Kalliopi and Trougakos, Ioannis P. and Kolettas, Evangelos and Georgakilas, Alexandros G. and Volarevic, Sinisa and Eliopoulos, Aristides G. and Zannis-Hadjopoulos, Maria and Moustakas, Aristidis and Gorgoulis, Vassilis G., "Cdc6 expression represses E-cadherin transcription and activates adjacent replication origins," The Journal of Cell Biology 195, no. 7 (December 2011), http://hdl.handle.net/10342/5447 (accessed February 26, 2021).
    AMA:
    Sideridou, Maria, Zakopoulou, Roubini, Evangelou, Konstantinos, Liontos, Michalis, Kotsinas, Athanassios, Rampakakis, Emmanouil, Gagos, Sarantis, Kahata, Kaoru, Grabusic, Kristina, Gkouskou, Kalliopi, Trougakos, Ioannis P., Kolettas, Evangelos, Georgakilas, Alexandros G., Volarevic, Sinisa, Eliopoulos, Aristides G., Zannis-Hadjopoulos, Maria, Moustakas, Aristidis, Gorgoulis, Vassilis G.. Cdc6 expression represses E-cadherin transcription and activates adjacent replication origins. The Journal of Cell Biology. December 2011; 195(7) 1123-1140. http://hdl.handle.net/10342/5447. Accessed February 26, 2021.
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