Examining the Effects of BORIS on Human Telomere Regulation and Stability

Telomeres serve vital functions for ensuring the integrity and stability of all eukaryotic organisms with linear chromosomes. Cancer cells manipulate telomere physiology in order to immortalize themselves. However, the full landscape of mechanisms which serve to regulate telomere homeostasis and how cancer cells hijack these mechanisms to benefit their own survival is not well understood. Therefore, there is a need to better understand all of the factors which may serve to regulate telomere function, particularly in cancer cells. In humans, a transcription factor known as CTCF has been shown to affect telomere stability and integrity, via binding to subtelomeric CTCF binding sites and promoting the transcription of telomere repeat encoding RNA (TERRA). The absence of CTCF has been shown to lead to telomere instability phenotypes through loss of TERRA transcription and suggests it plays an essential role in telomere regulation in normal and cancer cells. CTCF has one known paralogue known as the brother of the regulator of imprinted sites (BORIS). Preliminary data suggests that BORIS can also bind to these subtelomeric CTCF binding sites. In this study, we investigated the potential of BORIS to bind to these subtelomeric sites and its effect on TERRA transcription and telomere stability. Here we present evidence of BORIS binding to the subtelomere and a decrease in TERRA transcription in BORIS expressing cells, suggesting a potential antagonistic role for BORIS in CTCF-mediated TERRA transcription. In addition, we found that BORIS expression status had no significant effect on promoting stability of telomere repeats as measured on metaphase chromosomes. The work presented in this manuscript provides preliminary evidence of BORIS modulation of telomere function and stability. Further studies are needed to fully understand the role of BORIS in regulation of telomeres in normal and cancer cells.