Stress, Transposons, and the Brain Epigenome

Abstract

Long thought to be transcriptionally silent junk, transposable elements (TEs) are emerging as sources of functional elements in mammalian genomes due to the introduction of modern deep sequencing techniques. They have begun to attract the attention of neuroscientists due to the observation that the brain appears to be a privileged environment for transposon activity. In the brain, TEs show active transposition and frequently interact with the epigenetic machinery during development and in response to environmental inputs like stress. Barbara McClintock, the discoverer of TEs, long asserted that these elements were an important part of the genomic control apparatus, particularly in response to stress to the organism. Recent work has shown that this observation was a prescient one, as stress shows the capacity to alter the activity of these elements in the brain, in some cases with both adaptive and pathogenic consequences. TEs have been recently implicated in a number of mental disorders including Rett syndrome, posttraumatic stress disorder (PTSD), and schizophrenia. TE-derived regulatory RNA may comprise one of the largest single classes of functional elements in our genome, a discovery which will have a profound effect on how gene-environment interactions are understood within the context of the nervous system and beyond.