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dc.contributor.authorYuan, Yuan
dc.contributor.authorWang, Qiu
dc.contributor.authorPaulk, Joshiawa Lanair James
dc.contributor.authorKubicek, Stefan
dc.contributor.authorKemp, Melissa M.
dc.contributor.authorAdams, Drew J.
dc.contributor.authorShamji, Alykhan Farid
dc.contributor.authorWagner, Bridget K.
dc.contributor.authorSchreiber, Stuart L.
dc.date.accessioned2013-10-24T19:19:37Z
dc.date.issued2012
dc.identifier.citationYuan, Yuan, Qiu Wang, Joshiawa Lanair James Paulk, Stefan Kubicek, Melissa M. Kemp, Drew J. Adams, Alykhan Farid Shamji, Bridget K. Wagner, and Stuart L. Schreiber. 2012. A small-molecule probe of the histone methyltransferase g9a induces cellular senescence in pancreatic adenocarcinoma. ACS Chemical Biology 7(7): 1152-1157.en_US
dc.identifier.issn1554-8929en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11210614
dc.description.abstractPost-translational modifications of histones alter chromatin structure and play key roles in gene expression and specification of cell states. Small molecules that target chromatin-modifying enzymes selectively are useful as probes and have promise as therapeutics, although very few are currently available. G9a (also named euchromatin histone methyltransferase 2 (EHMT2)) catalyzes methylation of lysine 9 on histone H3 (H3K9), a modification linked to aberrant silencing of tumor-suppressor genes, among others. Here, we report the discovery of a novel histone methyltransferase inhibitor, BRD4770. This compound reduced cellular levels of di- and trimethylated H3K9 without inducing apoptosis, induced senescence, and inhibited both anchorage-dependent and -independent proliferation in the pancreatic cancer cell line PANC-1. ATM-pathway activation, caused by either genetic or small-molecule inhibition of G9a, may mediate BRD4770-induced cell senescence. BRD4770 may be a useful tool to study G9a and its role in senescence and cancer cell biology.en_US
dc.description.sponsorshipChemistry and Chemical Biologyen_US
dc.language.isoen_USen_US
dc.publisherAmerican Chemical Societyen_US
dc.relation.isversionofdoi:10.1021/cb300139yen_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401036/pdf/en_US
dash.licenseLAA
dc.titleA Small-Molecule Probe of the Histone Methyltransferase G9a Induces Cellular Senescence in Pancreatic Adenocarcinomaen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalACS Chemical Biologyen_US
dash.depositing.authorSchreiber, Stuart L.
dc.date.available2013-10-24T19:19:37Z
dc.identifier.doi10.1021/cb300139y*
dash.contributor.affiliatedYuan, Yuan
dash.contributor.affiliatedShamji, Alykhan
dash.contributor.affiliatedPaulk, Joshiawa
dash.contributor.affiliatedSchreiber, Stuart


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