Cell-cycle-dependent structural transitions in the human CENP-A nucleosome in vivo

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Minh Bui - , National Institutes of Health (NIH) (Author)
  • Emilios K Dimitriadis - , National Institutes of Health (NIH) (Author)
  • Christian Hoischen - , Leibniz Institute on Aging - Fritz Lipmann Institute (Author)
  • Eunkyung An - , National Institutes of Health (NIH) (Author)
  • Delphine Quénet - , National Institutes of Health (NIH) (Author)
  • Sindy Giebe - , Leibniz Institute on Aging - Fritz Lipmann Institute (Author)
  • Aleksandra Nita-Lazar - , National Institutes of Health (NIH) (Author)
  • Stephan Diekmann - , National Institutes of Health (NIH) (Author)
  • Yamini Dalal - , National Institutes of Health (NIH) (Author)

Abstract

In eukaryotes, DNA is packaged into chromatin by canonical histone proteins. The specialized histone H3 variant CENP-A provides an epigenetic and structural basis for chromosome segregation by replacing H3 at centromeres. Unlike exclusively octameric canonical H3 nucleosomes, CENP-A nucleosomes have been shown to exist as octamers, hexamers, and tetramers. An intriguing possibility reconciling these observations is that CENP-A nucleosomes cycle between octamers and tetramers in vivo. We tested this hypothesis by tracking CENP-A nucleosomal components, structure, chromatin folding, and covalent modifications across the human cell cycle. We report that CENP-A nucleosomes alter from tetramers to octamers before replication and revert to tetramers after replication. These structural transitions are accompanied by reversible chaperone binding, chromatin fiber folding changes, and previously undescribed modifications within the histone fold domains of CENP-A and H4. Our results reveal a cyclical nature to CENP-A nucleosome structure and have implications for the maintenance of epigenetic memory after centromere replication.

Details

Original languageEnglish
Pages (from-to)317-326
Number of pages10
JournalCell
Volume150
Issue number2
Publication statusPublished - 20 Jul 2012
Peer-reviewedYes
Externally publishedYes

External IDs

Scopus 84864193502
PubMed 22817894
PubMedCentral PMC3592566

Keywords

Keywords

  • Autoantigens/chemistry, Cell Cycle, Centromere/metabolism, Centromere Protein A, Chromosomal Proteins, Non-Histone/chemistry, DNA Replication, DNA-Binding Proteins/metabolism, HEK293 Cells, HeLa Cells, Histones/chemistry, Humans, Models, Molecular, Nucleosomes/metabolism, Protein Structure, Tertiary