期刊
DEVELOPMENTAL CELL
卷 29, 期 1, 页码 7-19出版社
CELL PRESS
DOI: 10.1016/j.devcel.2014.03.004
关键词
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资金
- MOST National Key Basic Research Program [2011CBA01002, 2012CB911202]
- National Natural Science Foundation of China [31271587]
- Tianjin Science & Technology Planned Program [12JCZDJC24800]
- intramural Biomedical Research Foundation, Academy of Athens
- Howard Temin Award [K99/R00 NIH/NCI 5R00CA131560]
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.
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