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SHIELD: a platform for high-throughput screening of barrier-type DNA elements in human cells

Author

Listed:
  • Meng Zhang

    (University of Illinois at Urbana-Champaign
    University of Illinois at Urbana-Champaign)

  • Mary Elisabeth Ehmann

    (University of Illinois at Urbana-Champaign)

  • Srija Matukumalli

    (University of Illinois at Urbana-Champaign)

  • Aashutosh Girish Boob

    (University of Illinois at Urbana-Champaign
    University of Illinois at Urbana-Champaign)

  • David M. Gilbert

    (San Diego Biomedical Research Institute)

  • Huimin Zhao

    (University of Illinois at Urbana-Champaign
    University of Illinois at Urbana-Champaign
    University of Illinois at Urbana-Champaign)

Abstract

Chromatin boundary elements contribute to the partitioning of mammalian genomes into topological domains to regulate gene expression. Certain boundary elements are adopted as DNA insulators for safe and stable transgene expression in mammalian cells. These elements, however, are ill-defined and less characterized in the non-coding genome, partially due to the lack of a platform to readily evaluate boundary-associated activities of putative DNA sequences. Here we report SHIELD (Site-specific Heterochromatin Insertion of Elements at Lamina-associated Domains), a platform tailored for the high-throughput screening of barrier-type DNA elements in human cells. SHIELD takes advantage of the high specificity of serine integrase at heterochromatin, and exploits the natural heterochromatin spreading inside lamina-associated domains (LADs) for the discovery of potent barrier elements. We adopt SHIELD to evaluate the barrier activity of 1000 DNA elements in a high-throughput manner and identify 8 candidates with barrier activities comparable to the core region of cHS4 element in human HCT116 cells. We anticipate SHIELD could facilitate the discovery of novel barrier DNA elements from the non-coding genome in human cells.

Suggested Citation

  • Meng Zhang & Mary Elisabeth Ehmann & Srija Matukumalli & Aashutosh Girish Boob & David M. Gilbert & Huimin Zhao, 2023. "SHIELD: a platform for high-throughput screening of barrier-type DNA elements in human cells," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41468-3
    DOI: 10.1038/s41467-023-41468-3
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    References listed on IDEAS

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    1. Lars Guelen & Ludo Pagie & Emilie Brasset & Wouter Meuleman & Marius B. Faza & Wendy Talhout & Bert H. Eussen & Annelies de Klein & Lodewyk Wessels & Wouter de Laat & Bas van Steensel, 2008. "Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions," Nature, Nature, vol. 453(7197), pages 948-951, June.
    2. Jesse R. Dixon & Siddarth Selvaraj & Feng Yue & Audrey Kim & Yan Li & Yin Shen & Ming Hu & Jun S. Liu & Bing Ren, 2012. "Topological domains in mammalian genomes identified by analysis of chromatin interactions," Nature, Nature, vol. 485(7398), pages 376-380, May.
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