Developmental cell, 2014-04, Vol.29 (1), p.7-19
2014
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- Autor(en) / Beteiligte
- Titel
- Rif1 Maintains Telomere Length Homeostasis of ESCs by Mediating Heterochromatin Silencing
- Ist Teil von
- Developmental cell, 2014-04, Vol.29 (1), p.7-19
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2014
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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. [Display omitted] •Rif1 maintains telomere length homeostasis and chromosomal stability of ESCs•Rif1 suppresses Zscan4 to prevent hyper telomere recombination•Rif1 interacts with and stabilizes the H3K9 methylation complex•Rif1 facilitates epigenetic silencing at subtelomeric heterochromatin Dan et al. uncover a role for telomere-associated protein Rif1 in the maintenance of telomere length homeostasis and genomic stability in mouse ESCs and during early embryonic development. Rif1 modulates sporadic Zscan4 expression, important for telomere elongation by recombination, by stabilizing subtelomeric heterochromatin and thereby prevents hyper telomere recombination.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1534-5807eISSN: 1878-1551DOI: 10.1016/j.devcel.2014.03.004Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4720134
- Format
- –
- Schlagworte
- Animals, Embryonic Stem Cells - metabolism, Embryonic Stem Cells - physiology, Gene Deletion, Gene Expression Regulation, Developmental, Gene Silencing, Heterochromatin - genetics, Heterochromatin - metabolism, Histones - metabolism, Methylation, Mice, Protein Binding, Protein Processing, Post-Translational, Recombination, Genetic, RNA, Messenger - genetics, RNA, Messenger - metabolism, Telomere - genetics, Telomere - metabolism, Telomere Homeostasis, Telomere-Binding Proteins - genetics, Telomere-Binding Proteins - metabolism, Transcription Factors - genetics, Transcription Factors - metabolism