Middle-down and top-down mass spectrometric analysis of co-occurring histone modifications

Rosalynn C. Molden, Benjamin A. Garcia

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Histones are chromatin proteins that are highly modified with many different types of post-translational modifications. These modifications act in concert to regulate a number of chromatin-related processes. However, identification and quantification of co-occurring histone post-translational modifications is challenging because there are many potential combinations of modifications and because the commonly used strategy of fragmenting proteins using trypsin or an alternative protease prior to LC-MS/MS analysis results in the loss of connectivity between modifications on different peptides. In this unit, mass spectrometric methods to analyze combinatorial histone modifications on histone tails (middle-down mass spectrometry) and on intact histones (top-down mass spectrometry) are described.

Original languageEnglish
Pages (from-to)23.7.1-23.7.28
JournalCurrent Protocols in Protein Science
StatePublished - 2014


  • Histone modifications
  • Middle-down mass spectrometry
  • Post-translational modifications
  • Top-down mass spectrometry


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