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<p>E-cadherin is a key determinant of epithelial tissue architecture, and its inhibition has been linked to transcriptional reprogramming and cellular plasticity in epithelial cancers. However, the chromatin-level mechanisms driving these changes remain incompletely understood. EP300, a histone acetyltransferase and transcriptional coactivator, has been implicated in mediating epigenetic responses to cell–cell adhesion loss. We examined the genome-wide chromatin binding profile of EP300 in MCF7 breast cancer cells following functional inhibition of E-cadherin using a neutralizing antibody. Chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) revealed 4128 EP300-enriched regions in control cells and 2943 in treated cells, with only 12 sites shared between conditions, indicating widespread redistribution. These changes localized to gene loci associated with epithelial identity (e.g., <i>CDH1</i>, <i>CD46</i>) and were replaced by increased occupancy at mesenchymal (<i>CDH2</i>, <i>LOX</i>) and pluripotency-associated loci (<i>SEMA3E</i>, <i>MET</i>). Differential binding was validated by chromatin immunoprecipitation coupled with quantitative polymerase chain reaction (ChIP–qPCR). Notably, EP300 protein levels remained unchanged, suggesting a redistribution rather than expression-level regulation. Our findings suggest that E-cadherin inhibition is associated with early changes in EP300 chromatin localization, particularly at loci linked to epithelial–mesenchymal transition (EMT) and pluripotency. These changes may reflect an early chromatin-level response to altered cell adhesion, warranting further functional investigation.</p>

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EP300 genomic redistribution following E-cadherin inhibition in MCF7 cancer cells: evidence for early epigenetic reprogramming

  • 期刊论文

  • 发表日期：

    2025年10月13日

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  • Hassan Kaabi,
  • Aseel Sharaireh,
  • Hanan Aljohani

摘要

E-cadherin is a key determinant of epithelial tissue architecture, and its inhibition has been linked to transcriptional reprogramming and cellular plasticity in epithelial cancers. However, the chromatin-level mechanisms driving these changes remain incompletely understood. EP300, a histone acetyltransferase and transcriptional coactivator, has been implicated in mediating epigenetic responses to cell–cell adhesion loss. We examined the genome-wide chromatin binding profile of EP300 in MCF7 breast cancer cells following functional inhibition of E-cadherin using a neutralizing antibody. Chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) revealed 4128 EP300-enriched regions in control cells and 2943 in treated cells, with only 12 sites shared between conditions, indicating widespread redistribution. These changes localized to gene loci associated with epithelial identity (e.g., CDH1, CD46) and were replaced by increased occupancy at mesenchymal (CDH2, LOX) and pluripotency-associated loci (SEMA3E, MET). Differential binding was validated by chromatin immunoprecipitation coupled with quantitative polymerase chain reaction (ChIP–qPCR). Notably, EP300 protein levels remained unchanged, suggesting a redistribution rather than expression-level regulation. Our findings suggest that E-cadherin inhibition is associated with early changes in EP300 chromatin localization, particularly at loci linked to epithelial–mesenchymal transition (EMT) and pluripotency. These changes may reflect an early chromatin-level response to altered cell adhesion, warranting further functional investigation.