No correlation between mtDNA amount and methylation levels at the CpG island of POLG exon 2 in wild-type and mutant human differentiated cells.
Steffann J, Pouliet A, Adjal H, Bole C, Fourrage C, Martinovic J, Rolland-Galmiche L, Rotig A, Tores F, Munnich A, Bonnefont JP.
Source : J. Med. Genet.
2018 Jan 8
Pmid : 28069933
METHODS: We have investigated the epigenetic modification of the POLG gene, by assessing the methylation level of its exon 2 using deep-Next Generation Sequencing analysis of bisulfite-treated DNA. Analysis were performed on various tissues at either postnatal or prenatal stages, on samples from carriers of mtDNA mutations, patients carrying two loss-of-function POLG mutations and controls.
RESULTS: Very high methylation levels at POLG exon 2 were found (94±3%) and no variation was observed according to either developmental stage or tissue of origin, except for sperm samples for which lower methylation levels were found (80%). This high level of methylation was neither correlated with the presence of mtDNA mutations (94±1% of methylated alleles), nor with biallelic POLG mutations (93%±2%), even in tissues where a mtDNA depletion had been observed.
CONCLUSIONS: This study suggests that, at variance with mouse and un/de-differentiated human cells, differentiated human cells control mtDNA levels irrespective of POLG methylation. The factors which actually control the mtDNA levels in such cell types remain to be identified.