Alu and LINE-1 are determinants for repressive mark type at genes and degree of gene expression level variation

Abstract

A fundamental unanswered question in biology is why the Alu transposable elements that constitute 11% of the human genome have amassed at varying levels in the vicinity of most genes and appear to have been selected against in non-gene regions while LINE-1 transposons that constitute 16% of the genome have accumulated around a minority of genes and are abundant in non-gene regions. Here we show that genes flanked by increasingly higher Alu concentrations display progressively less variation in expression level among humans and across human cell types while genes flanked by increasingly higher LINE-1 concentrations show progressively higher variation. Bayesian network modeling indicates that Alu elements promote H3K36me3 chromatin that fosters low gene expression variation while LINE-1 elements encourage H3K9me3 chromatin that procures high expression variation. Accordingly, genes in high Alu low LINE-1 environments produce H3K36me3 in their transcribed regions of at levels reflecting the levels of transcription while genes residing in progressively higher LINE-1 environments are increasingly likely to establish H3K9me3 in their transcribed regions, again at levels reflecting the levels of transcription. Further along these lines, silent genes occupied by repressive H3K36me3 across their regulatory regions reside primarily in high Alu low LINE-1 chromosomal environments, while occupation of silent genes by H3K9me3 is most prevalent in low Alu high LINE-1 environments, and genes silenced by H3K27me3 are concentrated in low Alu low LINE-1 environments. Genes residing in medium-high LINE-1 but extreme low Alu genes are exceptional as they tend to be occupied by an uncharacterized chromatin type. Finally, gene-distant regions are generally high LINE-1 low Alu, and here LINE-1 also promotes uncharacterized non-H3K9me3 chromatin that Alu opposes. Our findings indicate that local Alu and LINE-1 concentrations determine chromatin systems utilized by many genes.