Proteomics of a fuzzy organelle: interphase chromatin

EMBO J. 2014 Mar 18;33(6):648-64. doi: 10.1002/embj.201387614. Epub 2014 Feb 16.

Abstract

Chromatin proteins mediate replication, regulate expression, and ensure integrity of the genome. So far, a comprehensive inventory of interphase chromatin has not been determined. This is largely due to its heterogeneous and dynamic composition, which makes conclusive biochemical purification difficult, if not impossible. As a fuzzy organelle, it defies classical organellar proteomics and cannot be described by a single and ultimate list of protein components. Instead, we propose a new approach that provides a quantitative assessment of a protein's probability to function in chromatin. We integrate chromatin composition over a range of different biochemical and biological conditions. This resulted in interphase chromatin probabilities for 7635 human proteins, including 1840 previously uncharacterized proteins. We demonstrate the power of our large-scale data-driven annotation during the analysis of cyclin-dependent kinase (CDK) regulation in chromatin. Quantitative protein ontologies may provide a general alternative to list-based investigations of organelles and complement Gene Ontology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Artificial Intelligence
  • Cell Cycle Proteins / classification
  • Cell Cycle Proteins / genetics*
  • Centrifugation
  • Chromatin / genetics*
  • Cyclin-Dependent Kinases / genetics
  • Cyclin-Dependent Kinases / metabolism*
  • DNA-Binding Proteins / genetics*
  • Electrophoresis, Polyacrylamide Gel
  • Flow Cytometry
  • Gene Expression Regulation / genetics*
  • Gene Ontology
  • Humans
  • Interphase / genetics*
  • Mass Spectrometry
  • Models, Biological
  • Molecular Sequence Annotation
  • Proteomics / methods*

Substances

  • Cell Cycle Proteins
  • Chromatin
  • DNA-Binding Proteins
  • Cyclin-Dependent Kinases