Genomic Repeats Categorize Genes with Distinct Functions for Orchestrated Regulation

Cell Rep. 2020 Mar 10;30(10):3296-3311.e5. doi: 10.1016/j.celrep.2020.02.048.

Abstract

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.

Keywords: B1 or Alu; L1; L1 RNA; SINE; gene function; gene silencing; low-complexity repeats; nucleolus and lamina-associated domains; regulation and expression; repetitive elements.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Nucleolus / genetics
  • Chromatin / metabolism
  • Embryonic Development / genetics
  • Embryonic Stem Cells / metabolism
  • Embryonic Stem Cells / ultrastructure
  • Gene Expression Regulation, Developmental*
  • Gene Ontology
  • Genome*
  • HEK293 Cells
  • Humans
  • K562 Cells
  • Mice
  • Models, Genetic
  • Nuclear Lamina / genetics
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • RNA / genetics
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Repetitive Sequences, Nucleic Acid / genetics*
  • Transcription, Genetic

Substances

  • Chromatin
  • Phosphoproteins
  • RNA-Binding Proteins
  • nucleolin
  • RNA