Nordor, A. V. | bioRxiv Science

bioRxiv2018

“Global Transcriptional Response to CRISPR/CAS9-AAV6 Based Genome Editing” Matches Transcriptional Response to Specific Small Molecule Perturbations

Cromer et al. [1] recently reported global transcriptional changes occuring in cells in response to CRISPR/Cas9 gene editing. Using a CD34+ hematopoietic and progenitor stem cell model, they observed differentially expressed genes enriched for immune, stress and apoptotic processes following treatment with a CRISPR/Cas9-AAV6 genome-editing system. Following treatment with Cas9s mRNA they observed transcriptional changes enriched for viral response as well as a downregulation of metabolic and cell cycle processes. Similarly, they observed a downregulation of metabolic processes in response to electroporation. Surprisingly, no enrichment for viral response genes was observed following treatment with AAV6 while minor transcriptional changes enriched for DNA damage signature occurred in response to Cas9/sgRNA ribonucleoprotein.

molecular biology↗

bioRxiv2017

The early pregnancy human placenta shares hypomethylation patterns characteristic of solid tumors

BackgroundThe placenta relies on phenotypes that are characteristic of cancer to successfully implant the embryo in the uterus during early pregnancy. Notably, it has to invade its host tissues, promote angiogenesis, while surviving hypoxia, and escape the immune system. Similarities in DNA methylation patterns between the placenta and cancers suggest that common epigenetic mechanisms may be involved in regulating these behaviors.\n\nResultsWe show here that megabase-scale patterns of hypomethylation distinguish first from third trimester chorionic villi in the placenta, and that these patterns mirror those that distinguish many tumors from corresponding normal tissues. We confirmed these findings in villous cytotrophoblasts isolated from the placenta and identified a time window at the end of the first trimester, when these cells come into contact with maternal blood as the likely time period for the methylome alterations. Furthermore, the large genomic regions affected by these patterns of hypomethylation encompass genes involved in pathways related to epithelial-mesenchymal transition (EMT), immune response and inflammation. Analyses of expression profiles corresponding to genes in these hypomethylated regions in colon adenocarcinoma tumors point to networks of differentially expressed genes previously implicated in carcinogenesis and placentogenesis, where nuclear factor kappa B (NF-kB) is a key hub.\n\nConclusionTaken together, our results suggest the existence of epigenetic switches involving large-scale changes of methylation in the placenta during pregnancy and in tumors during neoplastic transformation. The characterization of such epigenetic switches might lead to the identification of biomarkers and drug targets in oncology as well as in obstetrics and gynecology.

genomics↗