Impact of DLK1-DIO3 imprinted cluster hypomethylation in smoker patients with lung cancer.
// Sonia Molina-Pinelo 1, 2 , Ana Salinas 1 , Nicolas Moreno-Mata 2 , Irene Ferrer 1, 2 , Rocio Suarez 1, 2 , Eduardo Andres-Leon 1 , Manuel Rodriguez-Paredes 4, 5 , Julian Gutekunst 4 , Eloisa Jantus-Lewintre 6, 7 , Carlos Camps 8, 9 , Amancio Carnero 1 , Luis Paz-Ares 1, 2 1 Instituto de Biomedicina de Sevilla (IBIS) (HUVR, CSIC, Universidad de Sevilla), Sevilla, Spain 2 Medical Oncology Department, Hospital Universitario Doce de Octubre & Centro Nacional de Investigaciones Oncologicas (CNIO), Madrid, Spain 3 Thoracic Surgery Department, Hospital Universitario Virgen del Rocio, Sevilla, Spain 4 Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany…
Selective inhibition of HDAC6 regulates expression of the oncogenic driver EWSR1-FLI1 through the EWSR1 promoter in Ewing sarcoma
Ewing sarcoma (EWS) is an aggressive bone and soft tissue tumor of children and young adults in which the principal driver is a fusion gene, EWSR1-FLI1. Although the essential role of EWSR1-FLI1 protein in the regulation of oncogenesis, survival, and tumor progression processes has been described in-depth, little is known about the regulation of chimeric fusion-gene expression. Here, we demonstrate that the active nuclear HDAC6 in EWS modulates the acetylation status of specificity protein 1 (SP1), consequently regulating the SP1/P300 activator complex binding to EWSR1 and EWSR1-FLI1 promoters. Selective inhibition of HDAC6 impairs binding of the activator complex SP1/P300, thereby inducing…
The cellular growth rate controls overall mRNA turnover, and modulates either transcription or degradation rates of particular gene regulons
We analyzed 80 different genomic experiments, and found a positive correlation between both RNA polymerase II transcription and mRNA degradation with growth rates in yeast. Thus, in spite of the marked variation in mRNA turnover, the total mRNA concentration remained approximately constant. Some genes, however, regulated their mRNA concentration by uncoupling mRNA stability from the transcription rate. Ribosome-related genes modulated their transcription rates to increase mRNA levels under fast growth. In contrast, mitochondria-related and stress-induced genes lowered mRNA levels by reducing mRNA stability or the transcription rate, respectively. We also detected these regulations within th…