文章基本信息

标题：Identification of new ETV6 modulators through a high-throughput functional screening
本地全文：下载
作者：Benjamin Neveu ; Chantal Richer ; Pauline Cassart 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：3
页码：1-23
DOI：10.1016/j.isci.2022.103858
语种：English
出版社：Elsevier
摘要：SummaryETV6transcriptional activity is critical for proper blood cell development in the bone marrow. Despite the accumulating body of evidence linkingETV6malfunction to hematological malignancies, its regulatory network remains unclear. To uncover genes that modulateETV6repressive 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 ofETV6transcriptional target genes. We showed that the silencing ofAKIRIN1,COMMD9,DYRK4,JUNB,andSRP72led to an abrogation ofETV6repressive activity. We identified critical modulators of theETV6function which could participate in cellular transformation through theETV6transcriptional network.Graphical abstractDisplay OmittedHighlights•We develop a genome-wide shRNAs screen for ETV6 modulators•The screen uncovered 13 novel putative ETV6 modulator genes•The modulators demonstrated a broad impact on theETV6transcriptional network•T-ALL cells results suggest modulators are conserved in other cellular contextsMolecular biology; Cancer systems biology; Omics