CENP-A nucleosome clusters form rosette-like structures around HJURP during G1

Nat Commun. 2019 Sep 30;10(1):4436. doi: 10.1038/s41467-019-12383-3.

Abstract

CENP-A is an essential histone H3 variant that epigenetically marks the centromeric region of chromosomes. Here we show that CENP-A nucleosomes form characteristic clusters during the G1 phase of the cell cycle. 2D and 3D super-resolution microscopy and segmentation analysis reveal that these clusters encompass a globular rosette-like structure, which evolves into a more compact structure in late G1. The rosette-like clusters contain numerous CENP-A molecules and form a large cellular structure of ∼250-300 nm diameter with remarkably similar shapes for each centromere. Co-localization analysis shows that HJURP, the CENP-A chaperone, is located in the center of the rosette and serves as a nucleation point. The discovery of an HJURP-mediated CENP-A nucleation in human cells and its structural description provide important insights into the mechanism of CENP-A deposition and the organization of CENP-A chromatin in the centromeric region.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / physiology
  • Cell Line
  • Centromere / metabolism
  • Centromere / ultrastructure
  • Centromere Protein A / metabolism*
  • Centromere Protein A / ultrastructure*
  • Chromatin
  • Chromatin Assembly and Disassembly / physiology
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Epigenomics
  • G1 Phase / physiology*
  • HeLa Cells
  • Humans
  • Imaging, Three-Dimensional
  • Mice
  • Mice, Inbred C57BL / embryology
  • Molecular Chaperones / chemistry
  • Nucleosomes / metabolism*
  • Nucleosomes / ultrastructure
  • Optical Imaging

Substances

  • Centromere Protein A
  • Chromatin
  • DNA-Binding Proteins
  • HJURP protein, human
  • Molecular Chaperones
  • Nucleosomes