Fall is in the Air: DNA Methylation Regulates Seasonal Hormonal Changes in Hamsters.
Ah the fall…the leaves are changing color, you can feel a chill in the air, the days are getting shorter, and your libido is decreasing…wait, what?!? Well, maybe not in humans, but seasonal changes that affect the length of day, or photoperiod, can have a profound effect on reproductive behavior and hormone expression in seasonal breeding vertebrates, such as hamsters. The question of whether or not epigenetic changes can occur in response to shifting photoperiods is still relatively unknown. A recent study conducted by Dr. Stevenson and Dr. Prendergast from the University of Chicago reported that different photoperiods were associated with epigenetic changes not only in the DNA methylation status of a hypothalamic-derived enzyme, but in the expression of DNA methyltransferases as well.
The authors wanted to determine whether nocturnal pineal melatonin (MEL) expression, a protein that regulates the reproductive neuroendocrine system during winter months in Siberian hamsters, has an effect on DNA methylation and MEL-regulated hypothalamus-expressed enzymes deiodinase type II (DIO2) and deiodinase type III (DIO3). Previous studies determined that dio2 mRNA levels are elevated in long day (LD) photoperiods, such as summer, resulting in increased production of gonadotrophin. During short day (SD) photoperiods, similar to winter, dio3 mRNA levels are increased, which inhibits gonadotrophin secretion. The authors first sought to determine the DNA methylation status of the proximal promoter for dio3, along with mRNA levels of dio3 and DNA methyltransferases of hamsters in short day environments. They found that the percent of methylated CpG sites of dio3 proximal promoter were two- to three-fold lower in SD compared to LD hamsters. The authors also observed increased levels of dio3 mRNA, while dnmt1 and dnmt3b mRNA levels were decreased. Next, the authors wanted to explain the relationship between MEL and the DNA methylation changes associated with SD. To do this, LD hamsters were treated with exogenous MEL to mimic winter expression levels. Similar to SD hamsters, these animals exhibited increased dio3 mRNA levels, a decrease in dio2 mRNA expression, a reduction in dnmt3b, and a decrease in the number of methylated CpG sites of the dio3 proximal promoter, indicating the MEL is involved in the epigenetic regulation of both DNMT3b and DIO3 expression. Finally, the authors discovered that changes in DNA methylation and mRNA levels associated with SD were subjected to photorefractoriness, meaning they spontaneously reverted to LD physiology after a period of time. They observed that after 42 weeks in SD conditions, dio3 and dnmt3b mRNA levels, as well as the percent methylation of the dio3 promoter returned to the levels observed in LD hamsters.
The results of this study contribute to our expanding knowledge of the diverse, but yet extremely important function of DNA methylation and the genetic plasticity. This study also leads to some interesting questions regarding epigenetic control of hormone expression and fertility in humans. Maybe one day, some infertility issues can be resolved by simply understanding the reversible relationship between DNA methylation and hormone production.
Stevenson TJ, & Prendergast BJ (2013). Reversible DNA methylation regulates seasonal photoperiodic time measurement. Proceedings of the National Academy of Sciences of the United States of America, 110 (41), 16651-6 PMID: 24067648