Abnormal histone acetylase and deacetylase expression and function in lung inflammation.
Post-translational modifications in DNA and histone proteins are heritable changes that are not coded for in the DNA sequence itself but play an important role in the control of gene expression. These modifications include histone acetylation, methylation, ubiquitination, sumoylation and phosphorylation. These changes are not only critical for generating diversity of cell types during mammalian development, but are also important for maintaining the stability and integrity of the expression profiles of different cell types. Until recently, the study of human disease has focused on genetic mechanisms rather than on non-coding events. However, it is becoming increasingly clear that altered patterns of histone modifications can lead to several major pathologies. This review focuses on histone acetylation and its role in inflammatory gene expression. Interestingly, the expression and activity of enzymes that regulate this modification have been reported to be abnormal in the airways of patients with respiratory disease. Histone modifications, despite being heritable and stably maintained, are also potentially reversible and there is scope for the development of "epigenetic therapies" for disease.
Adcock
I M
IM
Airways Disease Section, National Heart and Lung Institute, Imperial College London, UK. ian.adcock@imperial.ac.uk
Lee
K-Y
KY
D000818:Animals; D044127:Epigenesis, Genetic; D015971:Gene Expression Regulation, Enzymologic; D051548:Histone Acetyltransferases / Q000096:biosynthesis*; D006655:Histone Deacetylases / Q000096:biosynthesis*; D006657:Histones / Q000737:chemistry*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008168:Lung / Q000473:pathology*; D008954:Models, Biological; D011499:Protein Processing, Post-Translational
D006657:Histones; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases