Organ-, sex- and age-dependent patterns of endogenous L1 mRNA expression at a single locus resolution

Abstract

Expression of L1 mRNA, the first step in the L1 copy-and-paste amplification cycle, is a prerequisite for L1-associated genomic instability. We used a reported stringent bioinformatics method to parse L1 mRNA transcripts and measure the level of L1 mRNA expressed in mouse and rat organs at a locus-specific resolution. This analysis determined that mRNA expression of L1 loci in rodents exhibits striking organ specificity with less than 0.8% of loci shared between organs of the same organism. This organ specificity in L1 mRNA expression is preserved in male and female mice and across age groups. We discovered notable differences in L1 mRNA expression between sexes with only 5% of expressed L1 loci shared between male and female mice. Moreover, we report that the levels of total L1 mRNA expression and the number and spectrum of expressed L1 loci fluctuate with age as independent variables, demonstrating different patterns in different organs and sexes. Overall, our comparisons between organs and sexes and across ages ranging from 2 to 22 months establish previously unforeseen dynamic changes in L1 mRNA expression in vivo. These findings establish the beginning of an atlas of endogenous L1 mRNA expression across a broad range of biological variables that will guide future studies.

Diversity of Harbinger-like Transposons in Teleost Fish Genomes

“…Harbinger and ISL2EU transposons were mainly expressed in the same tissues in these species, suggesting common mechanisms of activation and repression. Moreover, in the medaka, both Harbinger and ISL2EU transposons showed testis-biased expression in gonads ( Figure 7 ), as reported for other transposable elements in other organisms [ 45 , 46 ].…”

Analysis of epigenetic features characteristic of L1 loci expressed in human cells

“…One previously used explanation was that hypomethylation of L1 promoters that may occur in the tumor could have a broad impact on L1 loci expression. However, as expression of individual L1 elements is highly dependent on cellular context, as seen in various mouse tissues ( 33 ) and human cell lines ( 22 , 32 ) (Figure 1 ), our data demonstrate that a wide array of cancer-specific changes, including sequence rearrangements repositioning CTCF binding sites, individual interactions between L1 elements and their enhancers, or changes in RNA Pol II recruitment through transcriptional factors, influence expression of individual L1 loci.…”

“…Previous studies have determined that each cell type expresses only a small and fairly unique subset of genomic L1 loci ( 21 , 64 , 116 ). A strict, organ-specific expression of L1 loci is also observed in vivo ( 33 ). The number of expressed L1 loci is typically <1% of full-length L1 loci in most cell lines ( 22 ).…”

“…This is consistent with the finding that full-length L1 loci are deleterious and have been under purifying selection ( 127–129 ). This may well explain the strong cell-type and tissue-specific expression patterns from individual L1 loci ( 22 , 32 , 130 ) because expressing an L1 locus ubiquitously would be more deleterious.…”

“…Furthermore, recent efforts to characterize L1 mRNA expression at single locus resolution have determined that, in any given cell line, most L1 transcripts come from a few loci, including from loci of the L1Hs sub-family, the youngest and most active L1 sub-family ( 21 , 22 , 30–32 ). Studies of endogenous L1 mRNA expression in mouse organs determined that this finding is true in vivo because only different small sets of L1 loci are expressed in each organ ( 33 ). These data strongly support the potential that genomic environment influences which L1 loci can be expressed.…”