Rif1 Maintains Telomere Length Homeostasis of ESCs by Mediating Heterochromatin Silencing
Copyright policy )Rif1 Maintains Telomere Length Homeostasis of ESCs by Mediating Heterochromatin Silencing
Telomere length homeostasis is essential for genomic stability and unlimited self-renewal of embryonic stem cells (ESCs). We show that telomere-associated protein Rif1 is required to maintain telomere length homeostasis by negatively regulating Zscan4 expression, a critical factor for telomere elongation by recombination. Depletion of Rif1 results in terminal hyperrecombination, telomere length heterogeneity, and chromosomal fusions. Reduction of Zscan4 by shRNA significantly rescues telomere recombination defects of Rif1-depleted ESCs and associated embryonic lethality. Further, Rif1 negatively modulates Zscan4 expression by maintaining H3K9me3 levels at subtelomeric regions. Mechanistically, Rif1 interacts and stabilizes H3K9 methylation complex. Thus, Rif1 regulates telomere length homeostasis of ESCs by mediating heterochromatic silencing.
- University of Florida United States
- Yale University United States
- Biomedical Research Foundation of the Academy of Athens Greece
- State University System of Florida United States
- State Key Laboratory of Medicinal Chemical Biology China (People's Republic of)
Recombination, Genetic, Telomere-Binding Proteins, Gene Expression Regulation, Developmental, Telomere Homeostasis, Telomere, Methylation, Histones, Mice, Heterochromatin, Animals, Gene Silencing, RNA, Messenger, Protein Processing, Post-Translational, Embryonic Stem Cells, Gene Deletion, Developmental Biology, Protein Binding, Transcription Factors
Recombination, Genetic, Telomere-Binding Proteins, Gene Expression Regulation, Developmental, Telomere Homeostasis, Telomere, Methylation, Histones, Mice, Heterochromatin, Animals, Gene Silencing, RNA, Messenger, Protein Processing, Post-Translational, Embryonic Stem Cells, Gene Deletion, Developmental Biology, Protein Binding, Transcription Factors
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