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.
Highlights
Human beta defensins are 3–5 kDa polycationic peptides that are known for their antimicrobial activity against bacteria, fungi and viruses [1]
The results of the present study showed that HDAC1 controls the expression of DEFB1 in lung epithelial cells by regulating transcriptional accessibility at the DEFB1 promoter
We hypothesized that DEFB1 gene expression is regulated by histone deacetylases (HDACs) and analyzed the effect of the broad-spectrum HDAC inhibitor trichostatin A on DEFB1 gene expression
Summary
Human beta defensins are 3–5 kDa polycationic peptides that are known for their antimicrobial activity against bacteria, fungi and viruses [1]. Defensins are chemotactic attractants for immature dendritic cells and memory T cells [2]. Defensins stimulate mitosis in fibroblasts and epithelial cells [3]. They play important roles in innate and adaptive immunity. Beta defensin 1 (DEFB1) was the first human beta defensin isolated [4] and it is expressed throughout the respiratory epithelia [5] and other epithelia and immune cells [4,6,7]. Stage-dependent upregulation of DEFB1 expression has been observed in the lungs of patients diagnosed with COPD [13])
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
