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Non-Coding RNA 2016, 2(2), 4; doi:10.3390/ncrna2020004

HDAC Inhibition in Vascular Endothelial Cells Regulates the Expression of ncRNAs

1
Epigenetics in Human Health and Disease Laboratory, Baker IDI Heart and Diabetes Institute, 75 Commercial Road, The Alfred Medical Research and Education Precinct, Melbourne, VIC 3004, Australia
2
Department of Pathology, The University of Melbourne, Parkville, VIC 3052, Australia
3
Faculty of Medicine, Monash University, Melbourne, VIC 3168, Australia
*
Author to whom correspondence should be addressed.
Academic Editor: George A. Calin
Received: 10 May 2016 / Revised: 16 May 2016 / Accepted: 19 May 2016 / Published: 25 May 2016
(This article belongs to the Special Issue The Biology of Non-Coding RNAs and Metabolic Diseases)
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Abstract

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. View Full-Text
Keywords: non-coding RNA; epigenetics; HDAC inhibitors; histone acetylation; histone methylation; endothelial cells; vascular non-coding RNA; epigenetics; HDAC inhibitors; histone acetylation; histone methylation; endothelial cells; vascular
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Rafehi, H.; El-Osta, A. HDAC Inhibition in Vascular Endothelial Cells Regulates the Expression of ncRNAs. Non-Coding RNA 2016, 2, 4.

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