Lee A.C.L.Hsiao W.-C.Wright D.E.Chong S.Y.Leow S.K.Ho C.-T.Kao C.-F.Lo Y.-C.2019-07-162019-07-16201317564646https://scholars.lib.ntu.edu.tw/handle/123456789/414068Polymethoxyflavones (PMFs), such as nobiletin and tangeretin, have a high cellular uptake rate, on account of their hydrophobicity. Nobiletin has been shown to down-regulate inflammatory gene expression, and is thus considered a promising anti-inflammatory and anti-carcinogenic agent. Most proteins known to be affected by PMFs are cell cycle regulators and kinases. In the present study, we demonstrate that PMF-mediated induction of GADD45£\ partially underlies the anti-proliferative effect of PMF on colorectal cancer cells. PMF-mediated induction of GADD45£\ was found to be associated with chromatin remodeling events at a novel enhancer element residing at intron 1 of GADD45£\. Moreover, GADD45£\ transcription correlated with differential acetylation of lysines 14 and 27 of histone H3 (H3K14/27) following treatment with either nobiletin or tangeretin. PMF-induced changes in H3K27 acetylation, H2A.Z and CBP were observed at intron 1, but not at p53 response-elements of GADD45£\, suggesting that nobiletin/tangeretin-mediated GADD45£\ activation may be independent of p53. ? 2013 Elsevier Ltd.Epigenetic regulationGADD45£\NobiletinPolymethoxyflavonesTangeretin[SDGs]SDG3journal article10.1016/j.jff.2013.01.0032-s2.0-84876722185https://www.scopus.com/inward/record.uri?eid=2-s2.0-84876722185&doi=10.1016%2fj.jff.2013.01.003&partnerID=40&md5=740d73fbbf4eadfadbdad4dd17caeed4