Biochemical systems approaches for the analysis of histone modification readout

Monica Soldi, Michael Bremang, Tiziana Bonaldi

Research output: Contribution to journalArticle

Abstract

Chromatin is the macromolecular nucleoprotein complex that governs the organization of genetic material in the nucleus of eukaryotic cells. In chromatin, DNA is packed with histone proteins into nucleosomes. Core histones are prototypes of hyper-modified proteins, being decorated by a large number of site-specific reversible and irreversible post-translational modifications (PTMs), which contribute to the maintenance and modulation of chromatin plasticity, gene activation, and a variety of other biological processes and disease states. The observations of the variety, frequency and co-occurrence of histone modifications in distinct patterns at specific genomic loci have led to the idea that hPTMs can create a molecular barcode, read by effector proteins that translate it into a specific transcriptional state, or process, on the underlying DNA. However, despite the fact that this histone-code hypothesis was proposed more than 10. years ago, the molecular details of its working mechanisms are only partially characterized. In particular, two questions deserve specific investigation: how the different modifications associate and synergize into patterns and how these PTM configurations are read and translated by multi-protein complexes into a specific functional outcome on the genome. Mass spectrometry (MS) has emerged as a versatile tool to investigate chromatin biology, useful for both identifying and validating hPTMs, and to dissect the molecular determinants of histone modification readout systems. We review here the MS techniques and the proteomics methods that have been developed to address these fundamental questions in epigenetics research, emphasizing approaches based on the proteomic dissection of distinct native chromatin regions, with a critical evaluation of their present challenges and future potential. This article is part of a Special Issue entitled: Molecular mechanisms of histone modification function.

Original languageEnglish
Pages (from-to)657-668
Number of pages12
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume1839
Issue number8
DOIs
Publication statusPublished - 2014

Fingerprint

Histone Code
Histones
Chromatin
Post Translational Protein Processing
Proteomics
Mass Spectrometry
Proteins
Mass spectrometry
Macromolecular Substances
Biological Phenomena
Genes
Nucleoproteins
Nucleosomes
Readout systems
DNA
Eukaryotic Cells
Dissection
Epigenomics
Transcriptional Activation
Plasticity

Keywords

  • Chromatin
  • Epigenetics
  • Histone code readers
  • Histone post-translational modification
  • Mass spectrometry
  • Proteomics

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Genetics
  • Molecular Biology
  • Structural Biology

Cite this

Biochemical systems approaches for the analysis of histone modification readout. / Soldi, Monica; Bremang, Michael; Bonaldi, Tiziana.

In: Biochimica et Biophysica Acta - Gene Regulatory Mechanisms, Vol. 1839, No. 8, 2014, p. 657-668.

Research output: Contribution to journalArticle

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