NIH Research Festival
The CCCTC-binding factor (CTCF) protein, a conserved architectural protein, shares its multivalent 11 ZnF DNA-binding domain with a paralogous counterpart named BORIS (a.k.a. CTCFL for ‚ÄúCTCF-like‚Äù). Although both proteins recognize the same variety of highly diverged target DNA sequences, they possess distinct N- and C-terminal domains interacting with specific protein partners to cause different functional outcomes. Recent studies have proposed testis-specific BORIS as a prognostic and therapeutic marker for ovarian cancers. Despite the high incidence of aberrant BORIS activation in ovarian cancers, its precise functional role remains elusive. In this study, we analyzed the impact of BORIS knockdown in ovarian cancer cells on chromatin status and transcriptional regulation, and observed extensive changes caused by BORIS K/O in genome-wide chromatin accessibility surrounding CTCF and BORIS co-binding sites. Transcriptome analysis revealed significant dysregulation of critical cancer-promoting transcription factors and signaling pathways. Intriguingly, we discovered that these changes in gene transcription occur in clusters, resulting in the simultaneous upregulation or downregulation of multiple adjacent genes. This suggests that the loss of BORIS impacts the 3D genome organization mediated by CTCF.
Our findings begun to shed light on the involvement of BORIS in ovarian cancer and its potential role in modulating chromatin regulation, transcriptional dysregulation, and 3D genome organization. Further investigation into the contribution of BORIS to 3D genome organization will provide valuable insights into the underlying mechanisms and may uncover novel therapeutic targets for ovarian cancer.
Scientific Focus Area: Cancer Biology
This page was last updated on Monday, September 25, 2023