title: ELF-MF exposure affects the robustness of epigenetic programming during granulopoiesis.
abstract: Extremely-low-frequency magnetic fields (ELF-MF) have been classified as "possibly carcinogenic" to humans on the grounds of an epidemiological association of ELF-MF exposure with an increased risk of childhood leukaemia. Yet, underlying mechanisms have remained obscure. Genome instability seems an unlikely reason as the energy transmitted by ELF-MF is too low to damage DNA and induce cancer-promoting mutations. ELF-MF, however, may perturb the epigenetic code of genomes, which is well-known to be sensitive to environmental conditions and generally deranged in cancers, including leukaemia. We examined the potential of ELF-MF to influence key epigenetic modifications in leukaemic Jurkat cells and in human CD34+ haematopoietic stem cells undergoing in vitro differentiation into the neutrophilic lineage. During granulopoiesis, sensitive genome-wide profiling of multiple replicate experiments did not reveal any statistically significant, ELF-MF-dependent alterations in the patterns of active (H3K4me2) and repressive (H3K27me3) histone marks nor in DNA methylation. However, ELF-MF exposure showed consistent effects on the reproducibility of these histone and DNA modification profiles (replicate variability), which appear to be of a stochastic nature but show preferences for the genomic context. The data indicate that ELF-MF exposure stabilizes active chromatin, particularly during the transition from a repressive to an active state during cell differentiation.
authors.affiliation: Department of Biomedicine, University of Basel, Mattenstrasse 28, Basel, CH-4058, Switzerland.
authors.forename: Melissa
authors.initials: M
authors.lastname: Manser
authors.affiliation: Swiss Tropical and Public Health Institute, Socinstrasse 57, Basel, CH-4002, Switzerland.|University of Basel, Petersplatz 1, Basel, CH-4001, Switzerland.|SIB Swiss Institute of Bioinformatics, Basel, Switzerland.
authors.forename: Mohamad R Abdul
authors.initials: MR
authors.lastname: Sater
authors.affiliation: Swiss Tropical and Public Health Institute, Socinstrasse 57, Basel, CH-4002, Switzerland.|University of Basel, Petersplatz 1, Basel, CH-4001, Switzerland.|SIB Swiss Institute of Bioinformatics, Basel, Switzerland.
authors.forename: Christoph D
authors.initials: CD
authors.lastname: Schmid
authors.affiliation: Department of Biomedicine, University of Basel, Mattenstrasse 28, Basel, CH-4058, Switzerland.|SIB Swiss Institute of Bioinformatics, Basel, Switzerland.
authors.forename: Faiza
authors.initials: F
authors.lastname: Noreen
authors.affiliation: IT'IS Foundation, Zeughausstrasse 43, Zürich, CH-8004, Switzerland.
authors.forename: Manuel
authors.initials: M
authors.lastname: Murbach
authors.affiliation: IT'IS Foundation, Zeughausstrasse 43, Zürich, CH-8004, Switzerland.|Swiss Federal Institute of Technology (ETH), Zürich, CH-8006, Switzerland.
authors.forename: Niels
authors.initials: N
authors.lastname: Kuster
authors.affiliation: Department of Biomedicine, University of Basel, Mattenstrasse 28, Basel, CH-4058, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Schuermann
authors.affiliation: Department of Biomedicine, University of Basel, Mattenstrasse 28, Basel, CH-4058, Switzerland.
authors.forename: Primo
authors.initials: P
authors.lastname: Schär
mesh_terms: D002454:Cell Differentiation / Q000528:radiation effects; D004247:DNA / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000528:radiation effects*; D006412:Hematopoietic Stem Cells / Q000528:radiation effects*; D006657:Histones / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells / Q000528:radiation effects*; D060526:Magnetic Fields; D008745:Methylation
chemical_list: D006657:Histones; D004247:DNA