Kids can be hard to handle, between dealing with drawing on the walls and public temper tantrums; therefore all parents need a successful tactic for keeping them under control. Short INterspersed Elements (SINEs) are like the chaotic kids of the genome. These repetitive sequences make up about 11% of our genome and because of their ability to copy and paste themselves, they can wreak havoc leading to mutations and chromosomal rearrangements if left unchecked.
Like a parent of hyperactive toddlers, the genome has strategies to keep them on a tight leash, but the exact mechanism is still a matter of debate. In the latest issue of Nature Communications, researchers led by Robert J. White reveal that it’s histone H3K9me3 and not DNA methylation (as previously thought) that acts as a pacifier to keep SINEs quiet.
Working with both HeLa cells and mouse fibroblasts, the researchers find that:
- SINEs are heavily methylated and bound by methyl-binding proteins.
- Despite heavy methylation, binding of RNA polymerase III and associated transcription factors is unaffected.
- Neither DNA demethylation by 5-azacytidine nor knockout of Dnmt1 leads to SINE expression.
- H3K9me3 is what keeps SINEs silenced as chemical inhibition of Suv39h1 leads to more RNA pol III recruitment and SINE expression.
Overall, the researchers suggest a mechanism of SINE silencing whereby H3K9me3 deposited by Suv39h1 or other H3K9 methyltransferases prevents loading of RNA pol III and hence, transcription. Although DNA methylation seems surplus to requirements for this H3K9me3-mediated silencing, they find that it has an important role is suppressing translocation of these parasites in our genome.
For more on the details, SINE up to Nature Communications and get the whole story: Nature Communications, March 2015
If regulation of RNA polymerases by histone modifications gets you all hot and bothered, check out Nature, December 2014; in this study researcher led by Hiroshi Kimura show how acetylation of histones regulates activation of RNA pol II.