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

作者：Wendong Yang, Zhiheng Zhang, Man-Yi Zhao, Ke Shao, Yanfeng Ma, Qi Shen, Meng-Ru Lu, Zhiying Shao, Jiayu Xu, Menghan Cao, Seng Meng, Sufang Chu, Hongmei Yong, Jin Ding, Jin Bai · 发表于：Communications Biology · 年份：2025 · DOI：10.1038/s42003-025-08430-z · 被引用次数：7 · 研究领域：Protein Degradation and Inhibitors、Histone Deacetylase Inhibitors Research、FOXO transcription factor regulation

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. This study highlights FOXQ1 as a key regulator of super enhancers, contributing to a deeper comprehension of FOXQ1-related tumours and bolstering the notion that FOXQ1 could be a potential target for colorectal cancer treatment