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Rapid profiling of transcription factor-cofactor interaction networks reveals principles of epigenetic regulation.
Inge, Melissa M; Miller, Rebekah; Hook, Heather; Bray, David; Keenan, Jessica L; Zhao, Rose; Gilmore, Thomas D; Siggers, Trevor.
Afiliación
  • Inge MM; Department of Biology, Boston University, Boston, MA 02215, USA.
  • Miller R; Biological Design Center, Boston University, Boston, MA 02215, USA.
  • Hook H; Department of Biology, Boston University, Boston, MA 02215, USA.
  • Bray D; Biological Design Center, Boston University, Boston, MA 02215, USA.
  • Keenan JL; Bioinformatics Program, Boston University, Boston, MA 02215, USA.
  • Zhao R; Department of Biology, Boston University, Boston, MA 02215, USA.
  • Gilmore TD; Department of Biology, Boston University, Boston, MA 02215, USA.
  • Siggers T; Bioinformatics Program, Boston University, Boston, MA 02215, USA.
Nucleic Acids Res ; 2024 Aug 21.
Article en En | MEDLINE | ID: mdl-39166482
ABSTRACT
Transcription factor (TF)-cofactor (COF) interactions define dynamic, cell-specific networks that govern gene expression; however, these networks are understudied due to a lack of methods for high-throughput profiling of DNA-bound TF-COF complexes. Here, we describe the Cofactor Recruitment (CoRec) method for rapid profiling of cell-specific TF-COF complexes. We define a lysine acetyltransferase (KAT)-TF network in resting and stimulated T cells. We find promiscuous recruitment of KATs for many TFs and that 35% of KAT-TF interactions are condition specific. KAT-TF interactions identify NF-κB as a primary regulator of acutely induced histone 3 lysine 27 acetylation (H3K27ac). Finally, we find that heterotypic clustering of CBP/P300-recruiting TFs is a strong predictor of total promoter H3K27ac. Our data support clustering of TF sites that broadly recruit KATs as a mechanism for widespread co-occurring histone acetylation marks. CoRec can be readily applied to different cell systems and provides a powerful approach to define TF-COF networks impacting chromatin state and gene regulation.

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Nucleic Acids Res Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Nucleic Acids Res Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido