Project description:This SuperSeries is composed of the following subset Series: GSE27968: DNA methylation data from AML12 cells during EMT GSE28291: Genome-scale epigenetic reprogramming during epithelial to mesenchymal transition Refer to individual Series
Project description:Epithelial-mesenchymal transition (EMT) involves profound changes in cell morphology, driven by transcriptional and epigenetic reprogramming. However, it emerges that translation and the ribosome composition play also key role in establishing physio-pathological phenotypes. Using genome-wide analyses, we report significant rearrangement of the translational landscape and machinery during EMT. Specifically, a mesenchymal cell line overexpressing the EMT transcription factor ZEB1 shows alterations in translational reprogramming and fidelity. Considering the change in translational activity of ZEB1-overexpressing mesenchymal cells, including in fidelity activity, we sought for changes in ribosome composition. We thus performed a riboproteome approach, i.e., mass spectrometry (MS)-based quantitative proteomic analysis of purified cytoplasmic ribosomes to highlight any change in relative amount of individual ribosomal proteins between wild-type and ZEB1-overexpressing human mammary epithelial cells.
Project description:Epithelial to mesenchymal transition (EMT) is an extreme example of cell plasticity, important for normal development, injury repair, and malignant progression. Widespread epigenetic reprogramming occurs during stem cell differentiation and malignant transformation, but EMT-related epigenetic reprogramming is poorly understood. Here we investigated epigenetic modifications during TGF-β-mediated EMT. While DNA methylation was unchanged during EMT, we found global reduction of the heterochromatin mark H3-lys9 dimethylation (H3K9Me2), increase of the euchromatin mark H3-lys4 trimethylation (H3K4Me3), and increase of the transcriptional mark H3-lys36 trimethylation (H3K36Me3). These changes were largely dependent on lysine-specific deaminase-1 (LSD1), and LSD1 loss-of-function experiments showed marked effects on EMT-driven cell migration and chemoresistance. Genome-scale mapping revealed that chromatin changes were largely specific to large organized heterochromatin K9-modifications (LOCKs), suggesting that EMT is characterized by reprogramming of specific chromatin domains across the genome.
Project description:The process of iPSC reprogramming involves various critical events such as somatic gene shutdown, mesenchymal-epithelial transition (MET), metabolism reprogramming, and epigenetic rewiring. These events interweave and influence each other leading to the formation of the iPSC reprogramming network, thus there appears to be a key element regulating this network. Dux has essential research value by promoting totipotency in the process of transition from ESC to 2C-like ESC and has not been discussed in depth in iPSC reprogramming process. This paper focused on the H3K18la modification linking the OGS-Epigenetic-MET network, which improved the efficiency for iPSC reprogramming via Dux overexpression. Dux promoted H3K18la via metabolism switch, and recruiting P300 through its C-terminal domain, resulting in increasing reprogramming. By using H3K18la regulators, we found the role H3K18la played in promoting MET. We performed proteomic detection of H3K18la by IP combined with MS and found that H3K18la specifically recruited Brg1 in iPSCs. During reprogramming, H3K18la and Brg1 enriched on promoters of epithelial-related genes and pluripotency-related genes. Overall, our work highlights H3K18la as a powerful trigger in the early reprogramming and reveals Dux as a regulator for increasing H3K18la. Brg1 was first demonstrated binding to H3K18la and identified as a reader of lactylation.