Cryoelectron tomography reveals the multiplex anatomy of condensed native chromatin and its unfolding by histone citrullination

Nathan Jentink, Carson Purnell, Brianna Kable, Matthew T. Swulius, Sergei A. Grigoryev

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Nucleosome chains fold and self-associate to form higher-order structures whose internal organization is unknown. Here, cryoelectron tomography (cryo-ET) of native human chromatin reveals intrinsic folding motifs such as (1) non-uniform nucleosome stacking, (2) intermittent parallel and perpendicular orientations of adjacent nucleosome planes, and (3) a regressive nucleosome chain path, which deviates from the direct zigzag topology seen in reconstituted nucleosomal arrays. By examining the self-associated structures, we observed prominent nucleosome stacking in cis and anti-parallel nucleosome interactions, which are consistent with partial nucleosome interdigitation in trans. Histone citrullination strongly inhibits nucleosome stacking and self-association with a modest effect on chromatin folding, whereas the reconstituted arrays undergo a dramatic unfolding into open zigzag chains induced by histone citrullination. This study sheds light on the internal structure of compact chromatin nanoparticles and suggests a mechanism for how epigenetic changes in chromatin folding are retained across both open and condensed forms.

Original languageEnglish (US)
Pages (from-to)3236-3252.e7
JournalMolecular cell
Volume83
Issue number18
DOIs
StatePublished - Sep 21 2023

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this