Silencing of Euchromatic Transposable Elements as a Consequence of Nuclear Lamina Dysfunction

• Main Authors: Valeria Cavaliere, Giovanna Lattanzi, Davide Andrenacci
• Format: Article
• Language: English
• Published: MDPI AG 2020-03-01
• Series: Cells
• Subjects: nuclear lamins; nuclear envelope; transposons; te silencing; gene expression; <i>lamdm0</i>; cosuppression
• Online Access: https://www.mdpi.com/2073-4409/9/3/625

Transposable elements (TEs) are mobile genomic sequences that are normally repressed to avoid proliferation and genome instability. Gene silencing mechanisms repress TEs by RNA degradation or heterochromatin formation. Heterochromatin maintenance is therefore important to keep TEs silent. Loss of heterochromatic domains has been linked to lamin mutations, which have also been associated with derepression of TEs. In fact, lamins are structural components of the nuclear lamina (NL), which is considered a pivotal structure in the maintenance of heterochromatin domains at the nuclear periphery in a silent state. Here, we show that a lethal phenotype associated with <i>Lamin</i> loss-of-function mutations is influenced by <i>Drosophila gypsy</i> retrotransposons located in euchromatic regions, suggesting that NL dysfunction has also effects on active TEs located in euchromatic loci. In fact, expression analysis of different long terminal repeat (LTR) retrotransposons and of one non-LTR retrotransposon located near active genes shows that <i>Lamin</i> inactivation determines the silencing of euchromatic TEs. Furthermore, we show that the silencing effect on euchromatic TEs spreads to the neighboring genomic regions, with a repressive effect on nearby genes. We propose that NL dysfunction may have opposed regulatory effects on TEs that depend on their localization in active or repressed regions of the genome.