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Published on: July 17, 2009
TRIM37 interacts with TRIM28 to maintain primordial germ cell identity during migration
Qing Li1,2, Xidi Yin3,4, Chuanyin Li5
1Key Laboratory of Multi-Cell Systems, Shanghai Key Laboratory of Molecular Andrology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. liqing2015@sibcb.ac.cn.
The E3 ubiquitin ligase TRIM37 safeguards primordial germ cell (PGC) fate by preventing somatic gene activation. TRIM37 deficiency leads to PGC loss and transition to somatic cells.
Area of Science:
- Developmental Biology
- Cell Biology
- Genetics
Background:
- Repressing somatic gene programs is crucial for establishing germline identity during primordial germ cell (PGC) specification.
- Mechanisms maintaining PGC fate after specification, particularly during migration, are not well understood.
Purpose of the Study:
- To identify molecular mechanisms that safeguard primordial germ cell (PGC) fate during their migration.
- To elucidate the role of the E3 ubiquitin ligase TRIM37 in maintaining PGC identity.
Main Methods:
- Investigated the function of TRIM37 in PGCs using knockout mouse models.
- Utilized biochemical assays to analyze TRIM37-TRIM28 interactions and ubiquitination.
- Assessed chromatin accessibility and histone modifications (H3K27ac) at somatic gene loci.
Main Results:
- TRIM37 deficiency results in severe PGC defects, including depletion by E12.5 and a shift towards somatic cell states.
- TRIM37 ubiquitinates TRIM28, enhancing their interaction and promoting TRIM37 nuclear retention, which is essential for PGC survival.
- The TRIM37-TRIM28 complex, with AP2γ, represses somatic transcriptional programs by restricting chromatin accessibility and H3K27ac at somatic gene loci.
Conclusions:
- TRIM37 acts as a critical safeguard of PGC fate during migration.
- A novel TRIM37-TRIM28-AP2γ complex prevents the activation of somatic transcriptional programs, thereby maintaining germ cell identity.
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