ELF‑MF exposure affects the robustness of epigenetic programming during granulopoiesis

Melissa Manser, Mohamad R. Abdul Sater, Christoph D. Schmid, Faiza Noreen, Manuel Murbach, Niels Kuster, David Schuermann, and Primo Schär, Scientific Reports 2017, Volume 7, Article number: 43345, online: 07 March 2017, DOI: 10.1038/srep43345.

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 leukemia. 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 disrupted in cancers, including leukemia. We examined the potential of ELF-MF to influence key epigenetic modifications in leukemic Jurkat cells and in human CD34+ hematopoietic 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 markers or in DNA methylation. However, ELF-MF exposure showed consistent effects on the reproducibility of these histone and DNA modification profiles, 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.

The scientific and technical impact of the study can be summarized as:

• The double-blinded exposure protocols of the sXcELF system were used for the first genome-wide profiling of the epigenetic genome modifications in EMF-MF-exposed human leukemic and differentiating hematopoietic cells
• No consistent effects of ELF-MF exposure on the patterning of key DNA and histone modifications (H3K4me2, H3K27me3, DNA cytosine methylation) in leukemic and differentiating hematopoietic cells were observed
• Genomic context-dependent differences in the reproducibility of genomic modification patterns suggest an influence of ELF-MF exposure on epigenetic plasticity

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