title: New Insights into the Role of Histone Deacetylases as Coactivators of Inflammatory Gene Expression.
abstract: CONCLUSIONS
  The expression and/or activity of histone deacetylases (HDACs) can be regulated by a variety of environmental conditions, including inflammation and oxidative stress. These events result in diminished or exaggerated protein acetylation, both of which can be causative for many ailments. While the anti-inflammatory activity of HDAC inhibitors (HDACis) is well known, recent studies started unraveling details of the molecular mechanisms underlying the pro-inflammatory function of HDACs.
  
  
  BACKGROUND
  Recent evidence shows that HDACs are found in association with transcribed regions and ensure proper transcription by maintaining acetylation homeostasis. We also discuss current insights in the molecular mechanisms mediating acetylation-dependent inhibition of pro-inflammatory transcription factors of the NF-κB, HIF-1, IRF, and STAT families.
  
  
  RESULTS
  The high number of acetylations and the complexity of the regulatory consequences make it difficult to assign biological effects directly to a single acetylation event. The vast majority of acetylated proteins are nonhistone proteins, and it remains to be shown whether the therapeutic effects of HDACis are attributable to altered histone acetylation.
  
  
  CONCLUSIONS
  In the traditional view, only exaggerated acetylation is harmful and causative for diseases. Recent data show the relevance of acetylation homeostasis and suggest that both diminished and inflated acetylation can enable the development of ailments. Since acetylation of nonhistone proteins is essential for the induction of a substantial part of the inflammatory gene expression program, HDACis are more than "epigenetic drugs." The identification of substrates for individual HDACs will be the prerequisite for the adequate use of highly specific HDACis.
authors.affiliation: 1 Medical Faculty, Institute of Biochemistry, Justus-Liebig-University , Giessen, Germany .|2 The German Center for Lung Research, Giessen, Germany .
authors.forename: Michael Lienhard
authors.initials: ML
authors.lastname: Schmitz
authors.affiliation: 3 Division of Cancer Research, Medical Research Institute, Jacqui Wood Cancer Centre, University of Dundee , Ninewells Hospital and Medical School, Dundee, United Kingdom .
authors.forename: Laureano
authors.initials: L
authors.lastname: de la Vega
mesh_terms: D000107:Acetylation; D000818:Animals; D044127:Epigenesis, Genetic; D015870:Gene Expression; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014157:Transcription Factors; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases