HiHiMap: single-cell quantitation of histones and histone posttranslational modifications across the cell cycle by high-throughput imaging

Mol Biol Cell. 2017 Aug 15;28(17):2290-2302. doi: 10.1091/mbc.E16-12-0870. Epub 2017 Jun 14.

Abstract

We describe High-throughput Histone Mapping (HiHiMap), a high-throughput imaging method to measure histones and histone posttranslational modifications (PTMs) in single cells. HiHiMap uses imaging-based quantification of DNA and cyclin A to stage individual cells in the cell cycle to determine the levels of histones or histone PTMs in each stage of the cell cycle. As proof of principle, we apply HiHiMap to measure the level of 21 core histones, histone variants, and PTMs in primary, immortalized, and transformed cells. We identify several histone modifications associated with oncogenic transformation. HiHiMap allows the rapid, high-throughput study of histones and histone PTMs across the cell cycle and the study of subpopulations of cells.

MeSH terms

  • Cell Cycle
  • Cell Division
  • Histones / analysis*
  • Histones / metabolism
  • Humans
  • Protein Processing, Post-Translational
  • Single-Cell Analysis / methods*
  • Tandem Mass Spectrometry / methods*

Substances

  • Histones