Abstract
Epigallocatechin gallate (EGCG), the main green tea polyphenol, exerts a wide variety of biological actions. Epigenetically, the catechin has been classified as a DNMTs inhibitor, however, its impact on histone modifications and chromatin structure is still poorly understood. The purpose of this study was to find the impact of EGCG on the histone posttranslational modifications machinery and chromatin remodeling in human endothelial cells of both microvascular (HMEC-1) and vein (HUVECs) origin. We analyzed the methylation and acetylation status of histones (Western blotting), as well as assessed the activity (fluorometric assay kit) and gene expression (qPCR) of the enzymes playing a prominent role in shaping the human epigenome. The performed analyses showed that EGCG increases histone acetylation (H3K9/14ac, H3ac), and methylation of both active (H3K4me3) and repressive (H3K9me3) chromatin marks. We also found that the catechin acts as an HDAC inhibitor in cellular and cell-free models. Additionally, we observed that EGCG affects chromatin architecture by reducing the expression of heterochromatin binding proteins: HP1α, HP1γ. Our results indicate that EGCG promotes chromatin relaxation in human endothelial cells and presents a broad epigenetic potential affecting expression and activity of epigenome modulators including HDAC5 and 7, p300, CREBP, LSD1 or KMT2A.
Highlights
Years of studies on natural compounds, i.e., sulphorafan, curcumin or ellagic acid, have revealed their potential for the development of more effective strategies for cancer prevention, support of organism regeneration after destructive cancer therapies, as well as the ability for the prevention and treatment of cardiovascular disorders [1,2,3,4]
Using two endothelial cell models, immortalized microvascular (HMEC-1) and primary vein (HUVECs), we studied the effect of EGCG on acetylation and methylation status of the core histone 3 (H3) and selected modifiers of the human epigenome, to figure out the role of green tea catechin in the regulation of chromatin conformation
We found that EGCG has no cytotoxic effects on both endothelial cell types
Summary
Years of studies on natural compounds, i.e., sulphorafan, curcumin or ellagic acid, have revealed their potential for the development of more effective strategies for cancer prevention, support of organism regeneration after destructive cancer therapies, as well as the ability for the prevention and treatment of cardiovascular disorders [1,2,3,4]. Growing evidence suggests that EGCG acts as a powerful antioxidant [6], inducing apoptosis and promoting tumor cell growth arrest by altering the expression of cell cycle regulatory proteins, activating caspases and suppressing NFκB transcriptional factor activation [7,8]. EGCG activates/inhibits several signaling pathways mainly by direct interaction with specific protein targets, including: (i) secreted proteases such as MMPs, (ii) membranes receptors, (iii) membrane microdomains, and (iv) the plasma membrane itself [8]. One of the first identified direct targets of EGCG was laminin. (Pin1) and transforming growth factor β receptor II (TGFR-II) [9,10,11,12]. The effects of EGCG on cellular metabolism are a consequence of its epigenetic properties
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