Proteomics in chromatin biology and epigenetics: Elucidation of post-translational modifications of histone proteins by mass spectrometry

Simone Sidoli, Lei Cheng, Ole N. Jensen

Research output: Contribution to journalReview article

96 Scopus citations

Abstract

Histone proteins contribute to the maintenance and regulation of the dynamic chromatin structure, to gene activation, DNA repair and many other processes in the cell nucleus. Site-specific reversible and irreversible post-translational modifications of histone proteins mediate biological functions, including recruitment of transcription factors to specific DNA regions, assembly of epigenetic reader/writer/eraser complexes onto DNA, and modulation of DNA-protein interactions. Histones thereby regulate chromatin structure and function, propagate inheritance and provide memory functions in the cell. Dysfunctional chromatin structures and misregulation may lead to pathogenic states, including diabetes and cancer, and the mapping and quantification of multivalent post-translational modifications has therefore attracted significant interest. Mass spectrometry has quickly been accepted as a versatile tool to achieve insights into chromatin biology and epigenetics. High sensitivity and high mass accuracy and the ability to sequence post-translationally modified peptides and perform large-scale analyses make this technique very well suited for histone protein characterization. In this review we discuss a range of analytical methods and various mass spectrometry-based approaches for histone analysis, from sample preparation to data interpretation. Mass spectrometry-based proteomics is already an integrated and indispensable tool in modern chromatin biology, providing insights into the mechanisms and dynamics of nuclear and epigenetic processes. This article is part of a Special Section entitled: Understanding genome regulation and genetic diversity by mass spectrometry.

Original languageEnglish (US)
Pages (from-to)3419-3433
Number of pages15
JournalJournal of Proteomics
Volume75
Issue number12
DOIs
StatePublished - Jun 27 2012
Externally publishedYes

Keywords

  • Bioinformatics
  • Chromatography
  • Epigenetics
  • Functional proteomics
  • Post-translational modifications
  • Tandem mass spectrometry

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

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