CENP-B-mediated DNA loops regulate activity and stability of human centromeres

Florian Chardon, Aleksandre Japaridze, Hannes Witt, Leonid Velikovsky, Camellia Chakraborty, Therese Wilhelm, Marie Dumont, Wayne Yang, Cees Dekker, More Authors

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Chromosome inheritance depends on centromeres, epigenetically specified regions of chromosomes. While conventional human centromeres are known to be built of long tandem DNA repeats, much of their architecture remains unknown. Using single-molecule techniques such as AFM, nanopores, and optical tweezers, we find that human centromeric DNA exhibits complex DNA folds such as local hairpins. Upon binding to a specific sequence within centromeric regions, the DNA-binding protein CENP-B compacts centromeres by forming pronounced DNA loops between the repeats, which favor inter-chromosomal centromere compaction and clustering. This DNA-loop-mediated organization of centromeric chromatin participates in maintaining centromere position and integrity upon microtubule pulling during mitosis. Our findings emphasize the importance of DNA topology in centromeric regulation and stability.

Original languageEnglish
Pages (from-to)1751-1767.e8
JournalMolecular Cell
Volume82
Issue number9
DOIs
Publication statusPublished - 2022

Bibliographical note

Accepted Author Manuscript

Keywords

  • AFM microscopy
  • CENP
  • centromere
  • chromosomes
  • DNA breaks
  • DNA compaction
  • DNA topology
  • genome stability
  • optical tweezers
  • secondary structures

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