Genomic repeats coordinate macroscopic gene function and expression

Despite abundant distribution of repetitive elements, the roles they have been coopted in mammalian genomes are insufficiently characterized. Here we reveal a pervasive role for genic repeat in shaping macroscopic gene function and expression in both human and mouse. Specifically, genes enriched in SINE, L1 and simple repeat produce proteins with functions in distinct categories. To maintain/regulate the homeostatic expression of gene with diversified functions, SINE and L1 are targeted by different classes of transcriptional regulators and also show a nonrandom genomic and nuclear distribution, with B1 in the nuclear interior and L1 in the nuclear and nucleolar peripheries. Abnormal expression of L1-enriched gene compromise proliferation of embryonic stem cells. Moreover, L1 transcripts tend to bind L1-enriched genes, transacting L1 DNA information and mainly function as transcriptional repressors. These results demonstrate that genomic repeats have subtly shaped the function of host-gene they embedded in, and provide a paradigm shift in understanding function of genomic “parasites” in their host-genome. ChIRP-seq of L1 and Malat1 RNA