Identification of new ETV6 modulators through a high-throughput functional screening

iScience

Chantal Richer¹  Pascal St-Onge²  Nicolas Garnier³  Benjamin Neveu⁴  Camille Jimenez-Cortes⁴  Claire Fuchs⁴  Stéphane Gobeil⁴  Maxime Caron⁴  Pauline Cassart⁴  Daniel Sinnett⁴ 

[1] Department of Biochemistry and Molecular Medicine, Faculty of Medicine, University of Montreal, Montreal, QC H3C 3J7, Canada;Department of Human Genetics, McGill University, Montréal, QC H3A 0C7, Canada;Molecular Biology Program, Faculty of Medicine, University of Montreal, Montreal, QC H3C 3J7, Canada;Sainte-Justine University Health Center Research Center, Montreal, QC H3T 1C5, Canada;

关键词: Molecular biology;    Cancer systems biology;    Omics;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: ETV6 transcriptional activity is critical for proper blood cell development in the bone marrow. Despite the accumulating body of evidence linking ETV6 malfunction to hematological malignancies, its regulatory network remains unclear. To uncover genes that modulate ETV6 repressive transcriptional activity, we performed a specifically designed, unbiased genome-wide shRNA screen in pre-B acute lymphoblastic leukemia cells. Following an extensive validation process, we identified 13 shRNAs inducing overexpression of ETV6 transcriptional target genes. We showed that the silencing of AKIRIN1, COMMD9, DYRK4, JUNB, and SRP72 led to an abrogation of ETV6 repressive activity. We identified critical modulators of the ETV6 function which could participate in cellular transformation through the ETV6 transcriptional network.

【 授权许可】

Unknown