Elevated H3K18 acetylation in airway epithelial cells of XXXX subjects.

@entity748 @entity32 @entity8850 @entity10319 @entity470 @entity565 @entity4206 @entity376
BACKGROUND: Epigenetic adjustments of the chromatin architecture through histone modifications are reactive to the environment and can establish chromatin states which are permissive or repressive to gene expression. Epigenetic regulation of gene expression is cell specific and therefore, it is important to understand its contribution to individual cellular responses in tissues like the airway epithelium which forms the mucosal barrier to the inhaled environment within the lung. The airway epithelium of @entity748 is abnormal with dysregulation of genes such as @entity470 ( @entity470 ), the   N isoform of the transcription factor @entity4206 (  Np63), and @entity8850 ( @entity8850 ), integral to differentiation, proliferation, and @entity32 . It is important to establish in diseases like @entity565 how histone modifications affect tissue responses such as proliferation and differentiation. OBJECTIVES: To characterize the global histone acetylation and methylation status in the epithelium of @entity748 compared to healthy subjects and to identify the impact of these variations on genes involved in epithelial functions. METHODS: Whole lungs were obtained from healthy and @entity748 subjects (n   =   6) from which airway epithelial cells (AECs) were isolated and airway sections were taken for analysis of histone @entity376 acetylation and methylation by immunohistochemistry. AECs were subjected to chromatin immunoprecipitation (ChIP) using anti-H3K18ac and anti-H3K4me2 antibodies followed by RT-PCR targeting   Np63, @entity470 , and @entity8850 . AECs were also treated with @entity10319 and changes in   Np63, @entity470 , and @entity8850 expression were determined. RESULTS: We identified an increase in the acetylation of @entity376 18 on histone 3 (H3K18ac) and trimethylation of @entity376 9 on histone 3 (H3K9me3) in the airway epithelium of @entity748 compared to healthy subjects. We found increased association of H3K18ac around the transcription start site of   Np63, @entity470 , and @entity8850 in AECs of @entity748 . However, we were unable to modify the expression of these genes with the use of the HDAC inhibitor @entity10319 in healthy subjects. DISCUSSION: The airway epithelium from @entity748 subjects displays increased acetylation of H3K18 and association of this mark around the transcription start site of   Np63, @entity470 , and @entity8850 . These findings suggest a complex interaction between histone modifications and gene regulation in @entity565 .
