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PTE, a novel module to target Polycomb Repressive Complex 1 to the human cyclin D2 (CCND2) oncogene
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
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2018 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 293, no 37, p. 14342-14358Article in journal (Refereed) Published
Abstract [en]

Polycomb group proteins are essential epigenetic repressors. They form multiple protein complexes of which two kinds, PRC1 and PRC2, are indispensable for repression. Although much is known about their biochemical properties, how mammalian PRC1 and PRC2 are targeted to specific genes is poorly understood. Here, we establish the cyclin D2 (CCND2) oncogene as a simple model to address this question. We provide the evidence that the targeting of PRC1 to CCND2 involves a dedicated PRC1-targeting element (PTE). The PTE appears to act in concert with an adjacent cytosine-phosphate-guanine (CpG) island to arrange for the robust binding of PRC1 and PRC2 to repressed CCND2. Our findings pave the way to identify sequence-specific DNA-binding proteins implicated in the targeting of mammalian PRC1 complexes and provide novel link between polycomb repression and cancer.

Place, publisher, year, edition, pages
American Society for Biochemistry and Molecular Biology, 2018. Vol. 293, no 37, p. 14342-14358
Keywords [en]
polycomb, epigenetics, gene silencing, chromatin, oncogene, cyclin D2, polycomb targeting, PRC1
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:umu:diva-152251DOI: 10.1074/jbc.RA118.005010ISI: 000444671500015PubMedID: 30068546OAI: oai:DiVA.org:umu-152251DiVA, id: diva2:1253309
Funder
Åke Wiberg FoundationMagnus Bergvall FoundationSwedish Cancer SocietySwedish Research CouncilKnut and Alice Wallenberg FoundationThe Kempe FoundationsAvailable from: 2018-10-04 Created: 2018-10-04 Last updated: 2019-02-12Bibliographically approved

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Cameron, Sarina R.Nandi, SoumyadeepKahn, Tatyana G.Stenberg, PerSchwartz, Yuri B.

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Cameron, Sarina R.Nandi, SoumyadeepKahn, Tatyana G.Barrasa, Juan I.Stenberg, PerSchwartz, Yuri B.
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Department of Molecular Biology (Faculty of Medicine)
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