| Literature DB >> 24735877 |
Jiameng Dan1, Yifei Liu2, Na Liu1, Maria Chiourea3, Maja Okuka4, Tao Wu2, Xiaoying Ye1, Chunlin Mou1, Lei Wang1, Lingling Wang1, Yu Yin1, Jihong Yuan1, Bingfeng Zuo1, Fang Wang1, Zhiguo Li1, Xinghua Pan2, Zhinan Yin1, Lingyi Chen1, David L Keefe5, Sarantis Gagos3, Andrew Xiao6, Lin Liu7.
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.Entities:
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Year: 2014 PMID： 24735877 PMCID： PMC4720134 DOI： 10.1016/j.devcel.2014.03.004
Source DB: PubMed Journal: Dev Cell ISSN： 1534-5807 Impact factor: 12.270