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A large-scale cancer-specific protein-DNA interaction network.
- Source :
-
Life science alliance [Life Sci Alliance] 2024 Jul 16; Vol. 7 (10). Date of Electronic Publication: 2024 Jul 16 (Print Publication: 2024). - Publication Year :
- 2024
-
Abstract
- 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.<br /> (© 2024 Lu et al.)
- Subjects :
- Humans
Promoter Regions, Genetic genetics
Oncogenes genetics
Prognosis
Estrogen Receptor alpha metabolism
Estrogen Receptor alpha genetics
Computational Biology methods
Neoplasms genetics
Neoplasms metabolism
Gene Expression Regulation, Neoplastic
Transcription Factors metabolism
Transcription Factors genetics
Gene Regulatory Networks
DNA metabolism
DNA genetics
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 2575-1077
- Volume :
- 7
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Life science alliance
- Publication Type :
- Academic Journal
- Accession number :
- 39013578
- Full Text :
- https://doi.org/10.26508/lsa.202402641