A new paper has just been published in the journal Genome Biology by John Rinn and David Kelley, identifying a role for transposable elements in gene regulation in stem cells. The authors summarize their results:
Our analysis of the TE composition of 9,241 human lincRNAs revealed that, in sharp contrast to protein coding genes, 83% of lincRNAs contain a TE, and TEs comprise 42% of lincRNA sequence. LincRNA TE composition varies significantly from genomic averages-L1 and Alu elements are depleted and broad classes of endogenous retroviruses are enriched. TEs occur in biased positions and orientations within lincRNAs, particularly at their transcription start sites, suggesting a role in lincRNA transcriptional regulation. Accordingly, we observed a dramatic example of HERVH transcriptional regulatory signals correlating strongly with stem cell specific expression of lincRNAs. Conversely, lincRNAs devoid of TEs are expressed at greater levels than lincRNAs with TEs in all tissues and cell lines, particularly in the testis.
Science Daily reports the paper:
Over a decade after sequencing the human genome, it has now become clear that the genome is not mostly “junk” as previously thought. In fact, the ENCODE project consortium of dozens of labs and petabytes of data have determined that these “noncoding” regions house everything from disease trait loci to important regulatory signals, all the way through to new types of RNA-based genes.
Yet over 70 years ago, it was first proclaimed that all this junk wasn’t so junky. Barbara McClintock discovered the first utility of all of this junk DNA: jumping genes, also known as transposable elements. These genes serve only one purpose, which is to replicate themselves and reinsert randomly in the genome, or do they? Ironically, at the same time two other scientists (Roy Britten and Eric Davidson) proposed that jumping genes may be involved in regulating cell specificity. Indeed, in an exciting new study published in Genome Biology, John Rinn and David Kelley based at Harvard University and the Broad Institute in Boston, USA, provide genome-wide evidence that jumping genes may shape when a gene is turned on or off in stem cells.
The study published by Rinn and Kelley finds a striking affinity for a class of hopping genes known as endogenous retroviruses, or ERVs, to land in lincRNAs. The study finds that ERVs are not only enriched in lincRNAs, but also often sit at the start of the gene in an orientation to promote transcription. Perhaps more intriguingly, lincRNAs containing an ERV family known as HERVH correlated with expression in stem cells relative to dozens of other tested tissues and cells. According to Rinn, “This strongly suggests that ERV transposition in the genome may have given rise to stem cell-specific lincRNAs. The observation that HERVHs landed at the start of dozens of lincRNAs was almost chilling; that this appears to impart a stem cell-specific expression pattern was simply stunning!”
Increasingly, this so-called parasitic “selfish” DNA appears to be quite otherwise. The more analysis is done, revealing function in the non-coding regions of our DNA, the more it turns out to be buzzing with activity.