Top-Performer: CRISPR/Cas9 Reveals Diverse Transcriptional Regulation and Functional Effects



October 5, 2021

Oncotarget published this trending research paper on August 17, 2021, entitled, “Diverse transcriptional regulation and functional effects revealed by CRISPR/Cas9-directed epigenetic editing” by researchers from the Division of Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Abstract: DNA methylation is an epigenetic process that controls DNA accessibility and serves as a transcriptomic switch when deposited at regulatory regions. The adequate functioning of this process is indispensable for tissue homeostasis and cell fate determination. Conversely, altered DNA methylation patterns result in abnormal gene transcription profiles that contribute to tumor initiation and progression. However, whether the consequence of DNA methylation on gene expression and cell fate is uniform regardless of the cell type or state could so far not been tested due to the lack of technologies to target DNA methylation in-situ. Here, we have taken advantage of CRISPR/dCas9 technology adapted for epigenetic editing through site-specific targeting of DNA methylation to characterize the transcriptional changes of the candidate gene and the functional effects on cell fate in different tumor settings. As a proof-of-concept, we were able to induce de-novo site-specific methylation of the gene promoter of IGFBP2 up to 90% with long-term and bona-fide inheritance by daughter cells. Strikingly, this modification led to opposing expression profiles of the target gene in different cancer cell models and affected the expression of mesenchymal genes CDH1, VIM1, TGFB1 and apoptotic marker BCL2. Moreover, methylation-induced changes in expression profiles was also accompanied by a phenotypic switch in cell migration and cell morphology. We conclude that in different cell types the consequence of DNA methylation on gene expression and cell fate can be completely different. Press release - Sign up for free Altmetric alerts about this article - DOI - Full text - Correspondence to - Miguel Vizoso - and Jacco van Rheenen - Keywords - targeted DNA methylation, CRISPR/Cas9-based system, IGFBP2, epithelial-to-mesenchymal transition About Oncotarget Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit or connect with: SoundCloud - Facebook - Twitter - LinkedIn - Pinterest - Reddit - Oncotarget is published by Impact Journals, LLC please visit or connect with @ImpactJrnls Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

Cancer Research

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