In vitro hydroquinone–induced instauration of histone bivalent mark on human retroelements (LINE-1) in HL60 cells. (April 2017)

• Record Type: Journal Article
• Authors: Mancini, Monica; Mandruzzato, Martina; Garzia, Alba C.; Sahnane, Nora; Magnani, Elena; Macchi, Filippo; Oulad-Abdelghani, Mustapha; Oudet, Pierre; Bollati, Valentina; Fustinoni, Silvia; Furlan, Daniela; Bonapace, Ian M.
• Is Part Of: Toxicology in vitro. Volume 40(2017)
• Page Start: 1
• Page End: 10
• Publication Date: 2017-04
• Subjects: LINE-1 or L1 long interspersed nuclear elements 1 -- HQ hydroquinone -- AML acute myeloid leukaemia -- DNMTs DNA methyl-transferases -- HMTs histone methyl-transferases; Benzene -- Histone modifications -- Bivalent mark -- DNA methylation -- AML -- LINE-1; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2016.12.007
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: Benzene is extensively used in industry despite its leukemogenic activity, representing a significant occupational hazard. We investigated if long-term treatment with low-doses hydroquinone (HQ), a benzene metabolite, might be sufficient to alter in vitro the epigenetic signature underlining LINE-1 sequences, a poorly explored step in health risks associated with benzene exposure. In HL-60 cell line, exploring the epigenetic events occurring in chromatin, we found the transient instauration of the distinctive signature combining the repressive H3Lys27 tri-methylation mark and the activating H3Lys4 tri-methylation mark (H3K27me3/H3K4me3), indicating a tendency toward a poised chromatin conformation. These alterations are lost in time after short-term treatments, while the long-term setting, performed using a concentration within the levels of total HQ in peripheral blood of benzene-exposed workers, showed a gradual increase in H3K4me3. We observed the absence of statistically significant variations in DNA methylation and expression levels of LINE-1, despite a decrease in protein levels of UHRF1, DNA methyl-transferases and histone methyl-transferases. In conclusion, in vitro treatment with low-dose HQ determined the instauration of a reversible poised state of chromatin in LINE-1 sequences, suggesting that prolonged exposure could cause persistent epigenetic alterations. Highlights: In vitro exposure to low-doses HQ can alter the epigenetic signature of AML cell line. In vitro treatments with low-doses HQ determine instauration of histone bivalent mark. In vitro exposures to low-doses HQ show no significant variation in DNA methylation on LINE-1. Epigenetic modifications after in vitro treatment with HQ are transitory and reversible.