Repetitive elements and epigenetic marks in behavior and psychiatric disease.

Abstract Repetitive elements, which are relics of previous transposition events, constitute a large proportion of the human genome. The ability of transposons to gives rise to new DNA combinations has clearly provided an evolutionary advantage to their hosts. Transposons have shaped our genomes by giving rise to novel coding sequences, alternative gene promoters, conserved noncoding elements, and gene networks. Despite its benefits, the process of transposition can also create deleterious DNA combinations, and a growing number of human diseases are being linked to abnormal repetitive element activity. To limit transposition, cells tightly regulate and immobilize repetitive elements using DNA methylation and other epigenetic marks. Recent findings in neuropsychiatric disorders implicate both repetitive elements and epigenetic marks as potential etiological factors. It is possible that these observations are linked and that the reported alterations in epigenetic marks may create a permissive state enabling transposons to mobilize. In this work, we provide a detailed description of repetitive element biology and epigenetics to familiarize the readers with the subject matter and to illustrate how their disruption can result in pathology. We also review the evidence for the involvement of these two factors in neuropsychiatric disorders and discuss the need for replication studies to confirm these initial findings. We are cautiously optimistic that further characterization of epigenetic mark and repetitive element activity in the brain will reveal the underlying causes of schizophrenia, bipolar disorder, and major depression.