RT Journal Article
SR Electronic
T1 A large-scale cancer-specific protein–DNA interaction network
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202402641
DO 10.26508/lsa.202402641
VO 7
IS 10
A1 Lu, Yunwei
A1 Berenson, Anna
A1 Lane, Ryan
A1 Guelin, Isabelle
A1 Li, Zhaorong
A1 Chen, Yilin
A1 Shah, Sakshi
A1 Yin, Meimei
A1 Soto-Ugaldi, Luis Fernando
A1 Fiszbein, Ana
A1 Fuxman Bass, Juan Ignacio
YR 2024
UL https://www.life-science-alliance.org/content/7/10/e202402641.abstract
AB Cancer development and progression are generally associated with gene dysregulation, often resulting from changes in the transcription factor (TF) sequence or expression. Identifying key TFs involved in cancer gene regulation provides a framework for potential new therapeutics. This study presents a large-scale cancer gene TF-DNA interaction network, as well as an extensive promoter clone resource for future studies. Highly connected TFs bind to promoters of genes associated with either good or poor cancer prognosis, suggesting that strategies aimed at shifting gene expression balance between these two prognostic groups may be inherently complex. However, we identified potential for oncogene-targeted therapeutics, with half of the tested oncogenes being potentially repressed by influencing specific activators or bifunctional TFs. Finally, we investigate the role of intrinsically disordered regions within the key cancer-related TF ESR1 in DNA binding and transcriptional activity, and found that these regions can have complex trade-offs in TF function. Altogether, our study broadens our knowledge of the TFs involved in cancer gene regulation and provides a valuable resource for future studies and therapeutics.All data generated in this study are available within the article and its supplementary information.