Abstract
Alu elements are primate-specific repeats and represent the most abundant type of transposable elements (TE) in the human genome. Genome-wide analysis of the enrichment of histone post-translational modifications suggests that human Alu sequences could function as transcriptional enhancers; however, no functional experiments have evaluated the role of Alu sequences in the control of transcription in situ. The present study analyses the regulatory activity of a human Alu sequence from the AluSx family located in the second intron of the long intergenic non-coding RNA Linc00441, found in divergent orientation to the RB1 gene. We observed that the Alu sequence acts as an enhancer element based on reporter gene assays while CRISPR-Cas9 deletions of the Alu sequence in K562 cells resulted in a marked transcriptional upregulation of Linc00441 and a decrease in proliferation. Our results suggest that an intragenic Alu sequence with enhancer activity can act as a transcriptional attenuator of its host lincRNA.
Highlights
Repetitive elements constitute ~50% of the human genome (Lander et al, 2001; Bannert and Kurth, 2004)
We hypothesized that the Alu sequences closest to the RB1 gene promoter could impact its transcriptional regulation via two general mechanisms
Induced epigenetic silencing, as it has been reported that young Alu elements are epigenetically repressed and Alu sequences can gain DNA methylation in cancer cells (Akers et al, 2014; Bakshi et al, 2016; Jorda et al, 2017) and secondly, transcription boosting by acting as enhancers, as has been proposed for old Alu families (Su et al, 2014)
Summary
Repetitive elements constitute ~50% of the human genome (Lander et al, 2001; Bannert and Kurth, 2004). The Alu subfamily of repetitive elements is a class of primate-specific Short Interspaced Nuclear Elements (SINEs) of ~300 base pair (bp) length that is present in more than 1 million copies in the human genome and constitutes the most abundant class of transposable element in humans (Lander et al, 2001). Their role in regulating gene expression and chromatin structure remains poorly characterized.
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