Transient co-expression of engineered transcriptional repressors (ETRs) allows for
stable and highly specific epigenetic silencing of endogenous genes, which is amenable
to multiplexing and can be reverted by targeted DNA demethylation.
Get Started for FREE
Sign up with Facebook Sign up with X
I don't have a Facebook or a X account
Your new post is loading...
Your new post is loading...
|
|
Here, the scientists repurpose the endogenous retroviruses’ silencing machinery of embryonic stem cells to stably silence three highly expressed genes in somatic cells by epigenetics. This was achieved by transiently expressing combinations of engineered transcriptional repressors that bind to and synergize at the target locus to instruct repressive histone marks and de novo DNA methylation, thus ensuring long-term memory of the repressive epigenetic state. Silencing was highly specific, as shown by genome-wide analyses, sharply confined to the targeted locus without spreading to nearby genes, resistant to activation induced by cytokine stimulation, and relieved only by targeted DNA demethylation.