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A large-scale cancer-specific protein-DNA interaction network.
Lu, Yunwei; Berenson, Anna; Lane, Ryan; Guelin, Isabelle; Li, Zhaorong; Chen, Yilin; Shah, Sakshi; Yin, Meimei; Soto-Ugaldi, Luis Fernando; Fiszbein, Ana; Fuxman Bass, Juan Ignacio.
Afiliación
  • Lu Y; https://ror.org/05qwgg493 Biology Department, Boston University, Boston, MA, USA.
  • Berenson A; https://ror.org/05qwgg493 Biology Department, Boston University, Boston, MA, USA.
  • Lane R; https://ror.org/05qwgg493 Molecular Biology, Cellular Biology and Biochemistry Program, Boston University, Boston, MA, USA.
  • Guelin I; https://ror.org/05qwgg493 Biology Department, Boston University, Boston, MA, USA.
  • Li Z; https://ror.org/05qwgg493 Biology Department, Boston University, Boston, MA, USA.
  • Chen Y; https://ror.org/05qwgg493 Bioinformatics Program, Boston University, Boston, MA, USA.
  • Shah S; https://ror.org/05qwgg493 Biology Department, Boston University, Boston, MA, USA.
  • Yin M; https://ror.org/05qwgg493 Biology Department, Boston University, Boston, MA, USA.
  • Soto-Ugaldi LF; https://ror.org/05qwgg493 Biology Department, Boston University, Boston, MA, USA.
  • Fiszbein A; Tri-Institutional Program in Computational Biology and Medicine, New York, NY, USA.
  • Fuxman Bass JI; https://ror.org/05qwgg493 Biology Department, Boston University, Boston, MA, USA.
Life Sci Alliance ; 7(10)2024 Oct.
Article en En | MEDLINE | ID: mdl-39013578
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Unión Proteica / Factores de Transcripción / ADN / Regulación Neoplásica de la Expresión Génica / Redes Reguladoras de Genes / Neoplasias Límite: Humans Idioma: En Revista: Life Sci Alliance Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Unión Proteica / Factores de Transcripción / ADN / Regulación Neoplásica de la Expresión Génica / Redes Reguladoras de Genes / Neoplasias Límite: Humans Idioma: En Revista: Life Sci Alliance Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos