Abstract
Previously, we reported on inter-individual and gender specific variations of LINE-1 methylation in healthy individuals. In this study, we investigated whether this variability could be influenced by age or sex hormones in humans. To this end, we studied LINE-1 methylation in vivo in blood-derived DNA from individuals aged 18 to 64 years and from young healthy females at various hormone levels during the menstrual cycle. Our results show that no significant association with age was observed. However, the previously reported increase of LINE-1 methylation in males was reconfirmed. In females, although no correlation between LINE-1 or Alu methylation and hormone levels was observed, a significant stable individual specific level of methylation was noted. In vitro results largely confirmed these findings, as neither estrogen nor dihydrotestosterone affected LINE-1 or Alu methylation in Hek293T, HUVEC, or MDA-kb2 cell lines. In contrast, a decrease in methylation was observed in estrogen-treated T47-Kbluc cell lines strongly expressing estrogen receptor. The very low expression of estrogen receptor in blood cells could explain the observed insensitivity of methylation at LINE-1 to natural hormonal variations in females. In conclusion, neither natural cycle of hormones nor age has a detectable effect on the LINE-1 methylation in peripheral blood cells, while gender remains an important factor.
Highlights
DNA methylation is an essential regulatory mechanism in gene expression
We looked at the methylation levels of LINE-1, using a degenerate amplification approach, and at F8 specific locus in about 300 healthy individuals ranging in age between 18-64 years
We addressed parameters that could possibly contribute to the variability of methylation, mainly at LINE-1 repetitive regions
Summary
In human adult somatic cells, it is present mainly at the 5th carbon position of cytosines in a CpG context, while in iPS and embryonic stem cells, it is present at non-CpG sites [1,2]. CpG sites in repetitive elements, like LINEs and Alus that constitute about 20% and 10% of the human genome, respectively [6,7,8], are largely methylated in normal somatic tissue. This is believed to suppress most of their transposition activity [9,10]. It has to be taken into account that not all L1 sequences in the genome are full length it is to be expected that only a fraction of the Line-1 repeats contain a CpG promoter rich region
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