MYCN and HIF-1 directly regulate expression to control 5-hmC gains and enhance neuroblastoma cell migration in hypoxia.

Ten-Eleven-Translocation 5-methylcytosine dioxygenases 1-3 (TET1-3) convert 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC), using oxygen as a co-substrate. Contrary to expectations, hypoxia induces 5-hmC gains in -amplified neuroblastoma (NB) cells via upregulation of . Here, we show that MYCN directly controls expression in normoxia, and in hypoxia, HIF-1 augments expression and TET1 protein stability.

5-Hydroxymethylcytosine Profiles Are Prognostic of Outcome in Neuroblastoma and Reveal Transcriptional Networks That Correlate With Tumor Phenotype.

Purpose: Whole-genome profiles of the epigenetic modification 5-hydroxymethylcytosine (5-hmC) are robust diagnostic biomarkers in adult patients with cancer. We investigated if 5-hmC profiles would serve as novel prognostic markers in neuroblastoma, a clinically heterogeneous pediatric cancer. Because this DNA modification facilitates active gene expression, we hypothesized that 5-hmC profiles would identify transcriptomic networks driving the clinical behavior of neuroblastoma.

Toward the Selective Inhibition of G Proteins: Total Synthesis of a Simplified YM-254890 Analog.

A simplified analog (WU-07047) of the selective Gαq/11 inhibitor YM-254890 has been synthesized, and an initial probe of its activity conducted. In the analog, the two peptide-based linkers in the cyclic YM-254890 have been replaced with hydrocarbon chains. This enables a convergent approach to the synthesis of the analog.

Microelectrode Arrays and the Use of PEG-Functionalized Diblock Copolymer Coatings.

PEG-modified diblock copolymer surfaces have been examined for their compatibility with microelectrode array based analytical methods. The use of PEG-modified polymer surfaces on the arrays was initially problematic because the redox couples used in the experiments were adsorbed by the polymer. This led the current measured by cyclic voltammetry for the redox couple to be unstable and increase with time.