title: In vitro hydroquinone-induced instauration of histone bivalent mark on human retroelements (LINE-1) in HL60 cells.
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.
authors.affiliation: Dept. of Biotechnologies and Life Sciences (DBSV), University of Insubria, via L. Manara 7, 21052 Busto Arsizio, Varese, Italy. Electronic address: monica.mancini@uninsubria.it.
authors.forename: Monica
authors.initials: M
authors.lastname: Mancini
authors.affiliation: Dept. of Biotechnologies and Life Sciences (DBSV), University of Insubria, via L. Manara 7, 21052 Busto Arsizio, Varese, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Mandruzzato
authors.affiliation: Dept. of Biotechnologies and Life Sciences (DBSV), University of Insubria, via L. Manara 7, 21052 Busto Arsizio, Varese, Italy.
authors.forename: Alba C
authors.initials: AC
authors.lastname: Garzia
authors.affiliation: Anatomic Pathology Unit, Dept. of Surgical and Morphological Sciences, University of Insubria, Via O. Rossi 9, 21100, Varese, Italy.
authors.forename: Nora
authors.initials: N
authors.lastname: Sahnane
authors.affiliation: Dept. of Biotechnologies and Life Sciences (DBSV), University of Insubria, via L. Manara 7, 21052 Busto Arsizio, Varese, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Magnani
authors.affiliation: Dept. of Biotechnologies and Life Sciences (DBSV), University of Insubria, via L. Manara 7, 21052 Busto Arsizio, Varese, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Macchi
authors.affiliation: Production of monoclonal and polyclonal antibodies, IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), Rue L. Fries, 1 - Illkirch Cedex, - 67400 Strasbourg, France.
authors.forename: Mustapha
authors.initials: M
authors.lastname: Oulad-Abdelghani
authors.affiliation: Département de Biologie du Cancer, IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire) (UMR 7104 CNRS, U596 INSERM, ULP), Rue L. Fries, 1 - Illkirch Cedex, - 67400 Strasbourg, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Oudet
authors.affiliation: EPIGET - Epidemiology, Epigenetics and Toxicology Lab - Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via S: Barnaba, 8, 20122 Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bollati
authors.affiliation: EPIGET - Epidemiology, Epigenetics and Toxicology Lab - Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via S: Barnaba, 8, 20122 Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Fustinoni
authors.affiliation: Anatomic Pathology Unit, Dept. of Surgical and Morphological Sciences, University of Insubria, Via O. Rossi 9, 21100, Varese, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Furlan
authors.affiliation: Dept. of Biotechnologies and Life Sciences (DBSV), University of Insubria, via L. Manara 7, 21052 Busto Arsizio, Varese, Italy. Electronic address: ian.bonapace@uninsubria.it.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Bonapace
mesh_terms: D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002843:Chromatin / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects; D018922:HL-60 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D006873:Hydroquinones / Q000633:toxicity*; D020084:Long Interspersed Nucleotide Elements / Q000187:drug effects*; D008780:Methyltransferases / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D002843:Chromatin; D006657:Histones; D006873:Hydroquinones; D008780:Methyltransferases; C406364:UHRF1 protein, human; D044767:Ubiquitin-Protein Ligases; C031927:hydroquinone
keywords: AML; Benzene; Bivalent mark; DNA methylation; Histone modifications; LINE-1