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.
|Titolo:||In vitro hydroquinone-induced instauration of histone bivalent mark on human retroelements (LINE-1) in HL60 cells|
|Parole Chiave:||AML; Benzene; Bivalent mark; DNA methylation; Histone modifications; LINE-1|
|Settore Scientifico Disciplinare:||Settore MED/44 - Medicina del Lavoro|
|Data di pubblicazione:||2017|
|Data ahead of print / Data di stampa:||13-dic-2016|
|Digital Object Identifier (DOI):||10.1016/j.tiv.2016.12.007|
|Appare nelle tipologie:||01 - Articolo su periodico|