Genomic Repeats Categorize Genes with Distinct Functions for Orchestrated Regulation

Summary: Repetitive elements are abundantly distributed in mammalian genomes. Here, we reveal a striking association between repeat subtypes and gene function. SINE, L1, and low-complexity repeats demarcate distinct functional categories of genes and may dictate the time and level of gene expression by providing binding sites for different regulatory proteins. Importantly, imaging and sequencing analysis show that L1 repeats sequester a large set of genes with specialized functions in nucleolus- and lamina-associated inactive domains that are depleted of SINE repeats. In addition, L1 transcripts bind extensively to its DNA in embryonic stem cells (ESCs). Depletion of L1 RNA in ESCs leads to relocation of L1-enriched chromosomal segments from inactive domains to the nuclear interior and de-repression of L1-associated genes. These results demonstrate a role of L1 DNA and RNA in gene silencing and suggest a general theme of genomic repeats in orchestrating the function, regulation, and expression of their host genes. : Lu et al. report a striking association between genomic repeats and gene regulation and demonstrate a key role of L1 repeat RNA in sequestering L1-rich sequences and associated genes in inactive domains for silencing, revealing a general theme of repeat sequences in shaping gene regulatory networks within their host genome. Keywords: repetitive elements, L1, B1 or Alu, SINE, low-complexity repeats, gene function, regulation and expression, nucleolus and lamina-associated domains, L1 RNA, gene silencing