| Popis: |
SUMMARYOct4 is a pioneer transcription factor regulating pluripotency. However, it is poorly known whether Oct4 has an impact on somatic cells. We generatedOCT4knockout clonal cell lines using immortalized human skin keratinocytes to identify a functional role for the protein. Here we report that Oct4-deficient cells transitioned into a mesenchymal-like phenotype with enlarged size and shape, exhibited accelerated migratory behavior, decreased adhesion and appeared arrested at G2/M cell cycle checkpoint. Oct4 absence had a profound impact on cortical actin organization, with loss of microfilaments from cell periphery, increased puncta deposition in the cytoplasm and stress fiber formation. E-cadherin, β-catenin and ZO1 were almost absent from cell-cell contacts while fibronectin deposition was markedly increased in ECM. Mapping of the transcriptional and chromatin profiles of Oct4-deficient cells revealed that Oct4 controls the levels of cytoskeletal, ECM and differentiation related genes, whereas epithelial identity is preserved through transcriptional and non-transcriptional mechanisms. |
