2. Academic Validation
  3. A PHF19-YTHDC1 condensate switches EZH2-mediated gene suppression to activation for prostate cancer progression

A PHF19-YTHDC1 condensate switches EZH2-mediated gene suppression to activation for prostate cancer progression

  • Proc Natl Acad Sci U S A. 2025 Oct 28;122(43):e2510386122. doi: 10.1073/pnas.2510386122.
Shuai Yuan # 1,  Dao-Jing Ming # 1 2,  Jiapeng He # 3,  Meng-Yang Liu # 1 2,  Shao-Hua He # 1 4,  Hong Weng 1 2,  Shu Xi 1 2,  Jin-Hui Zhang 1,  Ming-Hui Shi 1,  Jin-Long Cui 1 2,  Lu-Yao Li 1 2,  Haozhe Zhang 3,  Dan-Qi Wang 1 2,  Fei Li 1 2,  Meng-Meng Guo 1,  Yi Cai 1 2,  Shi-Di Tang 1 2,  Shuang-Ying Wang 1,  Xing-Huan Wang 1 2,  Xian-Tao Zeng 1 2 5,  Hailiang Hu 3
Affiliations

Affiliations

  • 1 Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
  • 2 Hubei Key Laboratory of Urinary System Diseases, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
  • 3 Department of Biochemistry, SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong 518000, China.
  • 4 Precision Medicine Center, The Second People's Hospital of Huaihua (Huaihua Cancer Hospital), Huaihua 418000, China.
  • 5 Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan 430071, China.
  • # Contributed equally.
PMID: 41129231 DOI: 10.1073/pnas.2510386122
Abstract

EZH2, a core component of PRC2 complex, silences global gene expression by tri-methylating histone H3K27. It remains an elusive question that EZH2 hyperexpression discords with its H3K27me3 activity of gene suppression in advanced prostate Cancer. Here, we report a nascent RNA-dependent PHF19-YTHDC1 condensate capable of switching EZH2-mediated gene suppression to activation during prostate Cancer progression. We found that the long isoform of PRC2 accessory subunit PHF19, PHF19L, was highly expressed in advanced prostate Cancer that promoted the tumor progression and hormonal therapy resistance. Mechanistically, PHF19L was recruited to the m6A modified nascent RNA through YTHDC1 and formed a liquid-like YTHDC1-PHF19L condensate that pulled the EZH2 away from chromatin, resulting in reduced H3K27me3 deposition and the activated expression of EZH2-repressed genes. Therefore, our study reveals a biomolecular condensate that modulates the switch from EZH2-mediated epigenetic gene silence to activation during the progression of prostate Cancer.

Keywords

EZH2; YTHDC1; liquid–liquid phase separation; nascent RNA; prostate cancer.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z