P300-dependent acetylation of the FOXQ1 complex activates super-enhancers to promote colorectal cancer proliferation and metastasis

Commun Biol. 2025 Jul 7;8(1):1016. doi: 10.1038/s42003-025-08430-z.

Abstract

The FOX transcription factor family plays a pivotal role in the malignant progression of tumors. We propose a hypothesis that FOXQ1 recruits p300 and BRD4 to super-enhancer regions. Our findings indicate that p300 acetylates Lys190 of FOXQ1, resulting in its recognition and binding by BRD4. Subsequently, BRD4 recruits RNA-Pol II to form a "FOXQ1-p300-BRD4-RNA Pol II" complex, which then binds to the super-enhancers of target genes. Meanwhile, acetylation at Lys190 of FOXQ1 directly enhances its binding affinity to super-enhancers. Consequently, more target oncogenes can be transcribed to promote CRC proliferation and metastasis. Our results suggest that FOXQ1 acts as a key regulator of super-enhancers, providing insights into its role in CRC and highlighting its potential as a therapeutic target.

MeSH terms

  • Acetylation
  • Animals
  • Bromodomain Containing Proteins
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / metabolism
  • Colorectal Neoplasms* / pathology
  • E1A-Associated p300 Protein* / genetics
  • E1A-Associated p300 Protein* / metabolism
  • Enhancer Elements, Genetic*
  • Forkhead Transcription Factors* / genetics
  • Forkhead Transcription Factors* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Neoplasm Metastasis
  • Transcription Factors / metabolism

Substances

  • Forkhead Transcription Factors
  • FOXQ1 protein, human
  • EP300 protein, human
  • E1A-Associated p300 Protein
  • Cell Cycle Proteins
  • BRD4 protein, human
  • Transcription Factors
  • Bromodomain Containing Proteins