Meeting Abstract
Transposons have played a significant role in the evolution of eukaryotic genomes, and exaptation of transposons has led to innovations such as the mammalian placenta and the adaptive immune system. Since McClintock’s discovery of what she called “controlling elements,” it has been evident that they tend to mobilize in response to stresses to the organism. This observation raises two questions: how does the genome control the stress-induced expression of transposons? Moreover, how do transposons detect stress? Much of the epigenetic machinery has been evolved to suppress or control these elements, and our work has shown the mammalian brain uses some of the same mechanisms of transposon control as have been observed in other organisms. We have shown that stress rapidly induces an increase in the repressive histone H3 lys9 trimethyl mark in the rat hippocampus. Further, corticosteroids themselves, acting via the glucocorticoid receptor (GR) act to increase the expression of B2 SINE and IAP-LTR retrotransposons, offering an answer to the question of how transposons detect organismal stress. Further, we have observed a potentially novel mechanism by which transposon derived RNA might serve to block GR action, leading to glucocorticoid resistance at the genomic level. Our observations that transposon expression varies substantially across sex suggest that sex steroids may also interact with these elements. There is abundant evidence that transposons and steroid receptors have been involved in an ancient interplay across vertebrate evolution. Roughly a third of the GR targets in the rat hippocampus are within or near transposons, and many steroid response elements in gene promoters are transposon derived. This data argues that, beyond their established role in genome evolution, transposons play day to day role in normal endocrine physiology.
