Middle-Down MS is Ready to Answer Complex Questions in Chromatin Biology

Research output: Contribution to journalComment/debate

1 Citation (Scopus)

Abstract

Histones are the most abundant protein family in the cells of complex organisms such as mammals and, together with DNA, they define the backbone of chromatin. Histone PTMs are key players of chromatin biology, as they function as anchors for proteins that bind and modulate chromatin readout, including gene expression. Middle-down mass spectrometry (MS) has been optimized for about 10 years to study histone N-terminal tails, but it has been rarely applied to identify the role of coexisting histone marks in biology. In this work, Jiang et al. used middle-down MS to study the dynamics of coexisting PTMs on histone H4 in two breast cancer cell lines. They found that overall serine 1 phosphorylation (S1ph) is mildly regulated during the cell cycle, but S1ph coexistence frequency with acetylations and methylations on the lysine residues of the N-terminal tail is remarkably tuned during S phase and G2/M phase. Together, the team placed another benchmark proving that MS analysis of combinatorial histone PTMs provides a more comprehensive view on chromatin state than studying individual marks. We should then constantly question ourselves regarding the limitations of analyzing single PTMs when we attempt to define their effect on protein functions.

Original languageEnglish (US)
Article number1800131
JournalProteomics
Volume18
Issue number13
DOIs
StatePublished - Jul 2018
Externally publishedYes

Fingerprint

Pulse time modulation
Histones
Chromatin
Mass spectrometry
Mass Spectrometry
Phosphorylation
Serine
Tail
Histone Code
Benchmarking
Cells
Proteins
G2 Phase
Acetylation
Methylation
Mammals
S Phase
Cell Division
Lysine
Anchors

Keywords

  • cancer
  • chromatin
  • histones
  • mass spectrometry
  • middle-down
  • posttranslational modifications

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Middle-Down MS is Ready to Answer Complex Questions in Chromatin Biology. / Sidoli, Simone.

In: Proteomics, Vol. 18, No. 13, 1800131, 07.2018.

Research output: Contribution to journalComment/debate

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