Endogenous retrovirus LTR12C hold potential locus-dependent activities as promoter and/or enhancer [RNA-seq]

Long terminal repeats (LTRs), which comprise promoter and enhancer region of intact endogenous retroviruses (ERVs), are known to be co-opted for fine-tuning host-coding gene expression as cis-regulatory elements. Since LTRs are mainly silenced by the deposition of repressive epigenetic marks, a substantial activation of LTRs have been found in human cells after treatment with epigenetic inhibitors. Although LTR12C family had highest relative abundance of transcripts among the de-repressed ERV families, functional consequences of the activated LTR12C for host-coding genes remain uncover due to genome-wide alteration of epigenetic landscape resulting in broad transcriptional changes after the epigenetic inhibitor treatments. Here, we transactivated more than 600 LTR12C elements by using single guide RNA-based dCas9-Suntag-VP64, which is a kind of the site-specific targeting technology CRISPR activation system, with minimal off-target events. Interestingly, most of transactivated LTR12C elements acquired H3K27ac-marked enhancer feature, while 20% of them along with enrichment of H3K4me3-marked promoter feature. The enrichment of H3K4me3 signal was likely brought about by downstream regions of LTR12C, such as internal regions of intact ERV9 or other type of retrotransposons.