RT Journal Article SR Electronic T1 Gene expression and chromatin accessibility during progressive EMT and MET linked to dynamic CTCF engagement JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.05.11.089110 DO 10.1101/2020.05.11.089110 A1 Kelsey S. Johnson A1 Shaimaa Hussein A1 Shuxuan Song A1 Priyanka Chakraborty A1 Mohit Kumar Jolly A1 Michael J. Toneff A1 Yin C. Lin A1 Joseph H. Taube YR 2020 UL http://biorxiv.org/content/early/2020/05/13/2020.05.11.089110.abstract AB Background Epithelial-mesenchymal transition (EMT) facilitates cellular movements critical for proper development; however, in a carcinoma, EMT promotes metastatic dissemination. Stable intermediate states (partial-EMT) are increasingly implicated in metastatic dissemination while reversal of EMT, termed mesenchymal-epithelial transition (MET), is increasingly implicated in metastatic colonization. To understand the partial and reversible nature of EMT, we characterized chromatin accessibility dynamics, transcriptome changes, protein expression patterns, as well as E-cadherin expression, localization, and gene-level dynamics in mammary epithelial cells undergoing stepwise reversible EMT.Results While shorter EMT induction induced internalization of E-cadherin protein, surface expression was recovered upon MET without loss of transcript or bulk protein. Conversely, a longer EMT induced stable repression of E-cadherin indicated by loss of chromatin accessibility and induced global expansion of accessible sites across the genome, facilitated by increased engagement of multiple transcription factor families, including AP-1 and SMAD. We observe enrichment for binding sites for the insulator proteins CTCF and BORIS was significantly diminished in both stemness-enriched partial-EMT and partial-MET states and determined that CTCF repression imparts alterations in some histone covalent modifications concomitant with those observed during TGFβ-induced EMT.Conclusions These findings are indicative of a major role for chromatin looping and reorganization in plasticity, stemness, and partial EMT phenotypes.Competing Interest StatementThe authors have declared no competing interest.