A good tailor will make any scientist look presentable in an expensive suit or a glitzy dress (when we escape the confines of a lab coat) and now, the group of Maria A. Blasco (CNIO, Madrid, Spain) describes how long non-coding RNAs (lncRNAs) tailor our telomeric DNA with just enough trimethylated histones to suit any catwalk or red carpet!
The lncRNAs in question, the TERRAs (telomeric repeat-containing RNAs), don´t derive from the bespoke garment-makers of Saville Row in London, but instead mainly arise from a single subtelomeric locus within the long arm of human chromosome 20. Multiple studies have implicated the telomere binding capabilities of TERRAs with various telomere maintenance-related functions, including heterochromatin formation and a previous study from the Blasco lab described a loss-of-function TERRA model (20q-TERRA knockout cells); a system tailor-made to delineate the exact mechanisms linking TERRA to heterochromatin formation at the telomeres.
Now, Montero and colleagues dazzle us with an array of bold colors, stark lines, and new findings that would surely wow any fashionista from Milan to Tokyo. Here is a taste of what they discovered:
- CRISPR-Cas9 mediated KO of 20q-TERRAs in human osteosarcoma cells inhibits the establishment of a trio of heterochromatin-associated trimethylated histones (H3K9me3, H4K20me3, and H3K27me3) at telomeric regions
- Furthermore, cells lacking TERRA expression also display shorter telomeres than control cells
- In normal cells, TERRA binds to the EZH2 (H3K27me3) and SUZ12 (H3K27me3 and H3K27me3) histone methyltransferases and brings the EZH2/SUZ12-containing Polycomb Repressive Complex 2 (PRC2) to telomeres
- PRC2 then catalyzes the deposition of the facultative heterochromatin-associated H3K27me3 modification
- The H3K27me3 modification then permits the establishment of the H3K9me3 and H4K20me3 modifications and promotes HP1 binding at telomeres
- However, the authors did not uncover a close relationship between TERRA status and telomeric- and global-DNA methylation levels
Overall, this stylish new study suggests that TERRA lncRNAs and PRC2 play a crucial role in creating the heterochromatin landscape at telomeric regions.
Do these new research findings “suit” you? To find out, read the full details of this exquisitely tailored study over at Nature Communications, April 2018.