DNA methylation and related mechanisms inhibit LINE-1 (L1) expression, and hypomethylation of DNA allows the L1 retrotransposon “life cycle” to proceed.

<p>In normal somatic cells, DNA methylation and related mechanisms inhibit LINE-1 (L1) expression (left image). In neoplastic cells, hypomethylation of DNA allows the L1 retrotransposon “life cycle” to proceed (right image). Retrotransposition is shown in a simplified schematic under the red box as (from left to right) transcription, assembly of ORF1p and ORF2p with L1 RNA, and insertion of a new L1 sequence (L1′). Related tumor effects are conceptually shown as (i) somatic retrotransposition of L1 and nonautonomous repeat elements, such as <i>Alu</i> repeats; (ii) transcriptional changes induced by L1-encoded promoters (in antisense and sense) or impacts on area methylation; and (iii) L1 ORF2p-generated DNA breaks. ASP, L1 antisense promoter.