TRIM66-HP1γ remodels the chromatin through phase separation
image: Model of chromatin condensation formation driven by TRIM66-HP1γ-H3K9me3 axis (The model was generated from BioRender.com)
Credit: Siyuan Shen, Feng Chen, Yifan Zhang, Fudong Li, Xuebiao Yao, Dan Liu, Yunyu Shi, Liang Zhang
Key Findings:
HP1γ interacts with TRIM66 through the PxVxL motif: Crystal structure analysis and binding affinity studies demonstrate a specific interaction between the chromo shadow domain (CSD) of HP1γ and the PxVxL motif of TRIM66.
TRIM66-HP1γ complexes form liquid droplets in vitro and in vivo: Live-cell imaging and in vitro assays confirm that TRIM66 and HP1γ can phase-separate together, forming dynamic liquid droplets within the nucleus.
TRIM66 BBCC domain is essential for phase separation: Deletion of the B-box-B-Box-Coil-Coil (BBCC) domain in TRIM66 abolishes its ability to induce phase separation, highlighting its critical role in this process.
TRIM66-HP1γ complex localizes to heterochromatin regions: Co-localization studies show that TRIM66-HP1γ complexes specifically accumulate in heterochromatin regions marked by H3K9me3.
TRIM66-HP1γ complex inhibits gene expression: Overexpression of TRIM66-HP1γ complexes leads to the suppression of gene expression in a reporter gene system, suggesting a role in transcriptional regulation.
Significance:
This study provides insights into the molecular mechanism by which TRIM66 and HP1γ remodel chromatin through LLPS. Understanding this process is crucial for comprehending the regulation of gene expression, maintenance of genomic stability, and potential implications in diseases associated with chromatin dysregulation.
The work entitled “TRIM66-HP1γ remodels the chromatin through phase separation”was published on Biophysics Reports (published on Feb, 2025).