The CTCF Paralog BORIS Contributes to the Ovarian Cancer Transcriptional Program by Relaxing CTCF-mediated 3D Genome Organization

Authors

Bhatt, D. N., Scott, A., Krymskaya, L., Markowitz, T. E., Price, E., Ji, Y., Loukinov, D., Traver, M., Brzostowski, J., Lobanenkov, V. V., Pugacheva, E. M.

Abstract

Disruption of three-dimensional genome architecture is a major driver of cancer initiation and progression, frequently arising from genetic and epigenetic alterations at CTCF- and cohesin-bound chromatin anchors. These same chromatin loop anchors can also be occupied by the germ cell-specific CTCF paralog CTCFL (BORIS), which is aberrantly activated in multiple malignancies. Here, we show that in ovarian cancer cells, BORIS activation establishes a distinct transcriptional program that collapses following loss of BORIS chromatin binding and is accompanied by widespread changes in CTCF and cohesin occupancy, histone modifications, and chromatin accessibility. These BORIS-dependent transcriptional alterations occur in long-range genomic clusters, resulting in the coordinated activation or repression of neighboring genes, including hormonally regulated gene families. BORIS loss also increases topologically associating domain (TAD) insulation, strengthens A/B compartment segregation and chromatin loop interactions, and results in a more compact and constrained chromatin architecture. Together, our findings suggest that aberrant BORIS activation promotes transcriptional reprogramming by weakening CTCF-mediated chromatin insulation and relaxing three-dimensional genome organization in ovarian cancer.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 06 Aug 2026.

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