Rif1 Maintains Telomere Length Homeostasis of ESCs by Mediating Heterochromatin Silencing

Jiameng Dan, Yifei Liu, Na Liu, Maria Chiourea, Maja Okuka, Tao Wu, Xiaoying Ye, Chunlin Mou, Lei Wang, Lingling Wang, Yu Yin, Jihong Yuan, Bingfeng Zuo, Fang Wang, Zhiguo Li, Xinghua Pan, Zhinan Yin, Lingyi Chen, David L. Keefe, Sarantis GagosAndrew Xiao, Lin Liu

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7-19
Number of pages13
JournalDevelopmental Cell
Volume29
Issue number1
DOIs
StatePublished - Apr 14 2014

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • Developmental Biology
  • Cell Biology

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