The 'Junk DNA' Paradigm Continues To Collapse As New Functions Are Discovered For Retrotransposons - Evolution News & Views

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The 'Junk DNA' Paradigm Continues To Collapse As New Functions Are Discovered For Retrotransposons

The literature continues to flood in demonstrating that so-called 'junk' regions of the genome are not junk after all, but serve significant and important functions. One such recent paper reports evidence that retrotransposons may play significant roles in the cell. According to the abstract,
Retrotransposons including endogenous retroviruses and their solitary long terminal repeats (LTRs) compose >40% of the human genome. Many of them are located in intergenic regions far from genes. Whether these intergenic retrotransposons serve beneficial host functions is not known. Here we show that an LTR retrotransposon of ERV-9 human endogenous retrovirus located 40--70 kb upstream of the human fetal γ- and adult β-globin genes serves a long-range, host function. The ERV-9 LTR contains multiple CCAAT and GATA motifs and competitively recruits a high concentration of NF-Y and GATA-2 present in low abundance in adult erythroid cells to assemble an LTR/RNA polymerase II complex. The LTR complex transcribes intergenic RNAs unidirectionally through the intervening DNA to loop with and modulate transcription factor occupancies at the far downstream globin promoters, thereby modulating globin gene switching by a competitive mechanism.
Retrotransposons include the long interspersed nuclear elements (LINEs), short interspersed nuclear elements (SINEs), endogenous retroviruses (ERVs), and the solitary long terminal repeats (LTRs) of ERVs, and compose over 40% of the human genome. Retrotransposons possess enhancers and promoters which promote the expression of downstream polycistronic gene sequences. The cited paper seeks to determine whether the retrotransposons which are located in the intergenic (regions which intersperse genes, also known as 'introns') of the genome - which are often several hundred kilobases removed from the promoters - serve any beneficial function.
The researchers, Pi et al. generated transgenic mice carrying an entire 100-kilobase human globin gene locus with or without the ERV-9 LTR, a class of retrotransposons found in human and chimpanzee globin gene loci, which possess enhancer and promoter activities in embryonic and hematopoetic progenitor cells. Deletion of the ERV-9 LTR resulted in suppression of the transcription of the β-globin gene and reactivated transcription of the γ-globin gene in adult erythroid cells in two of the lines of transgenic mice. The researchers concluded that "Locus-wide analysis of transcription factor occupancies, transcriptome status, and in vivo chromatin conformation provided unique experimental evidence that an intergenic retrotransposon serves a long-range beneficial host function." The paper's authors close their article by saying,
The ERV-9 LTR through its high-affinity binding of NF-Y may coordinate the transcriptional networks of these cis-linked genes during hematopoiesis. Thus, at least some of the 4,000 copies of the ERV-9 LTR retrotransposons distributed across the human chromosomes may serve a beneficial host function and may not be junk DNAs.

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