HDAC Inhibition in Vascular Endothelial Cells Regulates the Expression of ncRNAs

• Published in: Non-coding RNA Vol. 2; no. 2; p. 4
• Main Authors: Rafehi, Haloom, El-Osta, Assam
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25.05.2016; MDPI
• Subjects: Acetylation; Bioinformatics; Cancer; Clinical trials; Deacetylation; Deoxyribonucleic acid; Diabetes; DNA; DNA methylation; Endothelial cells; epigenetics; Gene expression; Genetic engineering; Genomes; HDAC inhibitors; histone acetylation; Histone deacetylase; histone methylation; Lysine; MicroRNAs; Non-coding RNA; Proteins; Ribonucleic acid; RNA; Transfer RNA; Trichostatin A; vascular; Australia; United States > US; histone methylation; endothelial cells; non-coding RNA; HDAC inhibitors; vascular; epigenetics; histone acetylation
• ISSN: 2311-553X; 2311-553X
• DOI: 10.3390/ncrna2020004

While clinical and pre-clinical trials indicate efficacy of histone deacetylase (HDAC) inhibitors in disease mediated by dynamic lysine modification, the impact on the expression of non-coding RNAs (ncRNAs) remains poorly understood. In this study, we investigate high throughput RNA sequencing data derived from primary human endothelial cells stimulated with HDAC inhibitors suberanilohydroxamic acid (SAHA) and Trichostatin A (TSA). We observe robust regulation of ncRNA expression. Integration of gene expression data with histone 3 lysine 9 and 14 acetylation (H3K9/14ac) and histone 3 lysine 4 trimethylation (H3K4me3) datasets identified complex and class-specific expression of ncRNAs. We show that EP300 target genes are subject to histone deacetylation at their promoter following HDAC inhibition. This deacetylation drives suppression of protein-coding genes. However, long intergenic non-coding RNAs (lincRNAs) regulated by EP300 are activated following HDAC inhibition, despite histone deacetylation. This increased expression was driven by increased H3K4me3 at the gene promoter. For example, elevated promoter H3K4me3 increased lincRNA MALAT1 expression despite broad EP300-associated histone deacetylation. In conclusion, we show that HDAC inhibitors regulate the expression of ncRNA by complex and class-specific epigenetic mechanisms.