OBJECTIVE To address the role of epigenetic enzymes in the process of arterial vasorelaxation and nitrate tolerance, in vitro and in vivo experiments were performed in the presence or absence of glyceryl trinitrate (GTN) or histone deacetylases/histone acetylases modulators. METHODS AND RESULTS In vitro single GTN administration rapidly increased cGMP synthesis and protein N(ε)-lysine acetyla...

Peptide motifs are often used for protein-protein interactions. We have recently demonstrated that ankyrin repeats of ANKRA2 and the paralogous bare lymphocyte syndrome transcription factor RFXANK recognize PxLPxL/I motifs shared by megalin, three histone deacetylases, and RFX5. We show here that that CCDC8 is a major partner of ANKRA2 but not RFXANK in cells. The CCDC8 gene is mutated in 3M sy...

A library of approximately 2000 small molecules biased toward inhibition of histone deacetylases was assayed for antimalarial activity in a high-throughput P. falciparum viability assay. Active compounds were cross-analyzed for induction of histone hyperacetylation in a human myeloma cell line to identify HDAC inhibitors with selectivity for P. falciparum over the human host. To verify on-targe...

⁎ Corresponding author at: Center for Therapeutic Innov atry & Behavioral Sciences, University of Miami Miller Sc 10th Ave, BRB-648 (M-860) Miami, FL 33136, USA. Tel.: + E-mail addresses: [email protected] (C.-H. Vol [email protected] (C. Wahlestedt). 1 Tel.: +1 305 243 7694. http://dx.doi.org/10.1016/j.nepig.2014.10.002 2214-7845/© 2014 The Authors. Published by Elsevier Inc Articl...

Histone acetylation and deacetylation play essential roles in modifying chromatin structure and regulating gene expression in eukaryotes. Histone deacetylases (HDACs) catalyze the deacetylation of lysine residues in the histone N-terminal tails and are found in large multiprotein complexes with transcriptional co-repressors. Human HDACs are grouped into three classes based on their similarity t...

Sir2 is a conserved deacetylase that modulates life span in yeast, worms, and flies and stress response in mammals. In yeast, Sir2 is required for maintaining replicative life span, and increasing Sir2 dosage can delay replicative aging. We address the role of Sir2 in regulating chronological life span in yeast. Lack of Sir2 along with calorie restriction and/or mutations in the yeast AKT homol...

Zhang, Wenzheng, and Bruce C. Kone. NFB inhibits transcription of the H -K -ATPase 2-subunit gene: role of histone deacetylases. Am J Physiol Renal Physiol 283: F904–F911, 2002. First published July 9, 2002; 10.1152/ ajprenal.00156.2002.—The H -K -ATPase 2 (HK 2) gene plays a central role in potassium homeostasis, yet little is known about its transcriptional control. We recently demonstrated t...

To probe the steric requirements for deacylation, we synthesized lysine-derived small molecule substrates and examined structure-reactivity relationships with various histone deacetylases. Rat liver, human HeLa, and human recombinant class I and II histone deacetylases (HDACs) as well as human recombinant NAD(+)-dependent SIRT1 (class III enzyme) were used in these studies. A benzyloxycarbonyl ...

Background. Mammalian erythroid cells undergo chromatin condensation and enucleation in their final stages of differentiation. We previously reported that Rac GTPases and their downstream target mDia2 are required for enucleation of in vitro cultured mouse fetal liver erythroblasts. However, it is not clear how chromatin condensation is achieved and whether it is required for enucleation. Desig...

Although histone acetylation is important for epigenetic gene transcription, histone acetylation regulation by extracellular cues has rarely been evidenced. Here, we examined whether and how histone acetylation is regulated by cell adhesion-mediated signaling. Gastric carcinoma cells in suspension showed a higher histone acetylation, compared with fibronectin-adherent cells. This difference was...