histone deacetylase (hdac) 1 controls the expression of beta defensin 1 in human lung epithelial cells组蛋白脱乙酰酶(hdac)1控制βdefensin 1的表达在人类肺上皮细胞.pdfVIP

Histone Deacetylase (HDAC) 1 Controls the Expression of Beta Defensin 1 in Human Lung Epithelial Cells Kimberley Kallsen, Ellen Andresen, Holger Heine* Division of Innate Immunity, Research Center Borstel, Airway Research Center North, Member of the German Center for Lung Research, Borstel, Germany Abstract Deregulation of the expression human beta defensin 1 (DEFB1), an antimicrobial peptide, has been implicated in the pathogenesis of COPD and asthma. Since the molecular mechanisms that regulate DEFB1 gene expression are widely unknown, the epigenetic processes involved in the regulation of the constitutive expression of DEFB1 in lung epithelial cells (A549) were investigated. The data demonstrate that histone deacetylases (HDACs) participate in the regulation of DEFB1 gene expression. Inhibition of the class I HDACs, HDACs 1-3, increases DEFB1 gene expression in A549 cells. Chromatin immunoprecipitation (ChIP) assays revealed that the inhibition of the class I HDACs also results in modifications of the chromatin at the DEFB1 promoter. Histone modifications, histone H3 acetylation and H3K4 trimethylation, that are associated with transcriptional activation, were found to increase after inhibition of HDACs 1-3. Finally, RNAi knockdown experiments identified HDAC1 as the sole HDAC responsible for maintaining the constitutive level of DEFB1 transcription. Taken together, our data reveal epigenetic mechanisms which are the basis of the maintenance of the constitutive gene expression of human beta defensin 1. Citation: Kallsen K, Andresen E, Heine H (2012) Histone Deacetylase (HDAC) 1 Controls the Expression of Beta Defensin 1 in Human Lung Epithelial Cells. PLoS ONE 7(11): e50000. doi:10.1371/journal.pone.0050000 ¨ Editor: Jurgen Harder, University Hospital Schleswi