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Updated: May 31, 2026

Mass Spectrometry Analysis to Identify Ubiquitylation of EYFP-tagged CENP-A (EYFP-CENP-A)
Published on: June 10, 2020
Non-centromeric CENP-A regulates epithelial-mesenchymal plasticity and heterogeneity in human cells
Charlène Renaud-Pageot1, Daniele Capocefalo2, Sébastien Lemaire1
1Institut Curie, Université PSL, Sorbonne Université, CNRS, UMR 3664 Nuclear Dynamics, Chromatin Dynamics Lab, Equipe Labellisée Ligue Contre le Cancer, 75005 Paris, France.
None:
Centromere protein A (CENP-A), a centromeric histone H3 variant highly expressed in aggressive cancers, promotes epithelial-mesenchymal transition (EMT), yet its underlying mechanisms remain unresolved. Here, we used a reversible high-CENP-A expression system in human cells to follow EMT-state trajectories and CENP-A localization over time. Sustained CENP-A elevation shifted hybrid populations toward mesenchymal states and increased both centromeric loading and ectopic chromatin incorporation. Chromatin immunoprecipitation revealed ectopic CENP-A enrichment at EMT-associated loci. Single-nucleus multi-omics further resolved two EMT programs engaged at distinct cell cycle stages: CENP-A strengthened a pre-existing inflammatory program and triggered a developmental program. Importantly, restoring basal CENP-A levels erased these transcriptional programs and eliminated ectopic incorporation, consistent with a reversible, non-genetic mechanism. Together, our findings uncover a non-centromeric function for CENP-A in shaping epithelial-mesenchymal plasticity and cellular heterogeneity.
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