LINE-1 creators of neuronal diversity

Abstract

Long interspersed nucleotide element 1 (L1) is a family of non-LTR retrotransposons that can replicate and reintegrate into the host genome. L1s have considerably influenced mammalian genome evolution by retrotransposing during germ cell development or early embryogenesis, leading to massive genome expansion. In humans, over 30 % of the genome can be attributed to L1-mediated retrotransposition. Historically, L1s were thought to only retrotranspose during gametogenesis and in neoplastic processes, but recent studies have shown that L1s are extremely active in the mouse, rat, and human neuronal progenitor cells (NPCs). In fact, it is estimated that the hippocampus and other regions of the brain may have multiple insertions per cell. These insertions can dramatically impact neuronal transcriptional expression, creating unique transcriptomes of individual neurons. Furthermore, transcriptional activation of L1 elements mimics the transcription activation of the NeuroD1 gene, suggesting a prominent role of L1 expression during neurogenesis.