CTCF contributes with α-satellite and satellite 2 expression in cancer cells: implications for centromeric chromatin organisation

BACKGROUND: The centromeric and pericentromeric regions of chromosomes are essential for genome stability. Beyond their structural role, noncoding RNAs (ncRNAs) transcribed from these regions have been implicated in kinetochore assembly. In cancer, reduced centromeric heterochromatin and deregulated ncRNA expression have been associated with chromosome instability. RESEARCH DESIGN AND METHODS: Centromeric and pericentromeric ncRNA expression was compared between the non-transformed WI-38 cell line and the colorectal cancer cell line HCT116. CTCF and H3K9me3 occupancy were evaluated by chromatin immunoprecipitation. Cells were treated with Trichostatin A (TSA), and CTCF function was assessed by pharmacological inhibition and shRNA-mediated depletion. RESULTS: Cancer cells exhibited elevated ncRNA levels, accompanied by reduced H3K9me3 enrichment and differential CTCF occupancy. Functional inactivation or depletion of CTCF markedly decreased ncRNA transcription, supporting a role for CTCF in regulating centromeric and pericentromeric ncRNAs. CONCLUSIONS: These findings support an association between chromatin state, CTCF occupancy, and ncRNA transcription at centromeric regions, and provide insight into epigenetic patterns associated with genome stability in cancer cells. Our results further suggest that centromeric chromatin operates within constrained transcriptional states compatible with chromosome stability.