Targeting transcription factor lysine acetylation in inflammatory airway diseases

Epigenomics. 2017 Jul;9(7):1013-1028. doi: 10.2217/epi-2017-0027. Epub 2017 Jun 15.

Abstract

Asthma and chronic obstructive pulmonary disease are inflammatory airway diseases for which alternative therapeutic strategies are urgently needed. Interestingly, HDAC inhibitors show anti-inflammatory effects in mouse models for these diseases. Here we explore underlying mechanisms that may explain these effects. In previous studies, effects of HDAC inhibitors on histone acetylation are often correlated with their effects on gene expression. However, effects of HDAC inhibitors on transcription factors and their acetylation status may be particularly important in explaining these effects. These effects are also cell type-specific. Recent developments (including chemoproteomics and acetylomics) allow for a more detailed understanding of the selectivity of HDAC inhibitors, which will drive their further development into applications in inflammatory airway diseases.

Keywords: COPD; acetylation; acetylomics; asthma; chemoproteomics; histone deacetylase; inhibitor; selectivity.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma / drug therapy
  • Asthma / genetics
  • Asthma / metabolism*
  • Histone Code / drug effects
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylase Inhibitors / therapeutic use
  • Humans
  • Pulmonary Disease, Chronic Obstructive / drug therapy
  • Pulmonary Disease, Chronic Obstructive / genetics
  • Pulmonary Disease, Chronic Obstructive / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Histone Deacetylase Inhibitors
  • Transcription Factors