• Home
  • Search Results
  • Endothelial transcriptome in response to pharmacological methyltransferase inhibition.

Endothelial transcriptome in response to pharmacological methyltransferase inhibition.

ChemMedChem (2014-05-23)
Jun Okabe, Ana Z Fernandez, Mark Ziemann, Samuel T Keating, Aneta Balcerczyk, Assam El-Osta
ABSTRACT

The enzymatic activities of protein methyltransferases serve to write covalent modifications on histone and non-histone proteins in the control of gene transcription. Here, we describe gene expression changes in human endothelial cells caused by treatment with methyltransferase inhibitors 7,7'-carbonylbis (azanediyl) bis(4-hydroxynaphthalene-2 -sulfonic acid (AMI-1) and disodium-2-(2,4,5,7- tetrabromo-3-oxido-6-oxoxanthen-9-yl) benzoate trihydrate (AMI-5). Deep sequencing of mRNA indicated robust change on transcription following AMI-5 treatment compared with AMI-1. Functional annotation analysis revealed that both compounds suppress the expression of genes associated with translational regulation, suggesting arginine methylation by protein arginine methyltransferases (PRMTs) could be associated with regulation of this pathway. Interestingly, AMI-5 but not AMI-1 was found to decrease methylation of H3 histones at lysine 4 and down-regulate gene expression associated with interleukin-6 (IL-6) and activator protein-1 (AP-1) signaling pathways. These results imply that inhibition of protein methylation by AMI-1 and AMI-5 can differentially regulate specific pathways with potential to interrupt pathological signaling in the vascular endothelium.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Sulfuric acid, ACS reagent, 95.0-98.0%
Sigma-Aldrich
Sulfuric acid, 99.999%
Sigma-Aldrich
Magnesium chloride, anhydrous, ≥98%
Sigma-Aldrich
Magnesium chloride solution, for molecular biology, 1.00 M±0.01 M
Sigma-Aldrich
Magnesium chloride solution, BioUltra, for molecular biology, ~1 M in H2O
Sigma-Aldrich
Ethylenediaminetetraacetic acid, ACS reagent, 99.4-100.6%, powder
Sigma-Aldrich
Ethylenediaminetetraacetic acid, BioUltra, anhydrous, ≥99% (titration)
Sigma-Aldrich
Ethylenediaminetetraacetic acid solution, BioUltra, for molecular biology, pH 8.0, ~0.5 M in H2O
Sigma-Aldrich
BIS-TRIS, ≥98.0% (titration)
Sigma-Aldrich
Sulfuric acid, puriss. p.a., for determination of Hg, ACS reagent, reag. ISO, reag. Ph. Eur., 95.0-97.0%
Sigma-Aldrich
Actinomycin D, from Streptomyces sp., ~98% (HPLC)
Sigma-Aldrich
Ethylenediaminetetraacetic acid, anhydrous, crystalline, BioReagent, suitable for cell culture
Sigma-Aldrich
BICINE, ≥99% (titration)
Sigma-Aldrich
Actinomycin D, from Streptomyces sp., suitable for cell culture, ≥95%
Sigma-Aldrich
Ethylenediaminetetraacetic acid solution, 0.02% in DPBS (0.5 mM), sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
BICINE, BioXtra, ≥99% (titration)
Sigma-Aldrich
Magnesium chloride, powder, <200 μm
Supelco
Sulfuric acid, for the determination of nitrogen, ≥97.0%
Supelco
Sulfuric acid concentrate, 0.1 M H2SO4 in water (0.2N), eluent concentrate for IC
Sigma-Aldrich
Magnesium chloride solution, BioUltra, for molecular biology, 2 M in H2O
Sigma-Aldrich
Ethylenediaminetetraacetic acid, purified grade, ≥98.5%, powder
Sigma-Aldrich
Ethylenediaminetetraacetic acid, 99.995% trace metals basis
SAFC
BIS-TRIS
Sigma-Aldrich
Magnesium chloride, BioReagent, suitable for insect cell culture, ≥97.0%
Sigma-Aldrich
Sulfuric acid, puriss., meets analytical specification of Ph. Eur., BP, 95-97%
Sigma-Aldrich
BIS-TRIS, BioXtra, ≥98.0% (titration)
Sigma-Aldrich
Magnesium chloride solution, PCR Reagent, 25 mM MgCI2 solution for PCR
Sigma-Aldrich
Ethylenediaminetetraacetic acid, ≥98.0% (KT)
Sigma-Aldrich
BIS-TRIS, BioUltra, ≥99.0% (NT)
Sigma-Aldrich
Ethylenediaminetetraacetic acid, BioUltra, ≥99.0% (KT)