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Essential role of Cp190 in physical and regulatory boundary formation.

  • Kaushal, Anjali1
  • Dorier, Julien2
  • Wang, Bihan1
  • Mohana, Giriram1
  • Taschner, Michael3
  • Cousin, Pascal1
  • Waridel, Patrice4
  • Iseli, Christian2
  • Semenova, Anastasiia1
  • Restrepo, Simon5
  • Guex, Nicolas2
  • Aiden, Erez Lieberman6, 7, 8, 9
  • Gambetta, Maria Cristina1
  • 1 Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland. , (Switzerland)
  • 2 Bioinformatics Competence Center, University of Lausanne, 1015 Lausanne, Switzerland. , (Switzerland)
  • 3 Department of Fundamental Microbiology, University of Lausanne, 1015 Lausanne, Switzerland. , (Switzerland)
  • 4 Protein Analysis Facility, University of Lausanne, 1015 Lausanne, Switzerland. , (Switzerland)
  • 5 arcoris bio AG, Lüssirainstrasse 52, 6300 Zug, Switzerland. , (Switzerland)
  • 6 The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA.
  • 7 National Institute of Genetics, 1111 Yaya, Mishima, Shizuoka 411-8540, Japan. , (Japan)
  • 8 UWA School of Agriculture and Environment, The University of Western Australia, Perth, WA 6009, Australia. , (Australia)
  • 9 Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech, Pudong 20120, China. , (China)
Published Article
Science Advances
American Association for the Advancement of Science (AAAS)
Publication Date
May 13, 2022
DOI: 10.1126/sciadv.abl8834
PMID: 35559678


Boundaries in animal genomes delimit contact domains with enhanced internal contact frequencies and have debated functions in limiting regulatory cross-talk between domains and guiding enhancers to target promoters. Most mammalian boundaries form by stalling of chromosomal loop-extruding cohesin by CTCF, but most Drosophila boundaries form CTCF independently. However, how CTCF-independent boundaries form and function remains largely unexplored. Here, we assess genome folding and developmental gene expression in fly embryos lacking the ubiquitous boundary-associated factor Cp190. We find that sequence-specific DNA binding proteins such as CTCF and Su(Hw) directly interact with and recruit Cp190 to form most promoter-distal boundaries. Cp190 is essential for early development and prevents regulatory cross-talk between specific gene loci that pattern the embryo. Cp190 was, in contrast, dispensable for long-range enhancer-promoter communication at tested loci. Cp190 is thus currently the major player in fly boundary formation and function, revealing that diverse mechanisms evolved to partition genomes into independent regulatory domains.

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