Rif1 Maintains Telomere Length Homeostasis of ESCs by Mediating Heterochromatin Silencing

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

doi:10.1016/j.devcel.2014.03.004

Cited by 117 publications

(132 citation statements)

References 57 publications

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“…Interestingly, Rif1 is known to interact with Sirt3, Sirt7 (40), and Setdb1 (41,42). Sirt3 and Sirt7 deacetylate histones, whereas Setdb1 methylates histone at H3-K9.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Regulation of the Blimp-1 Gene (Prdm1) in B Cells Involves Bach2 and Histone Deacetylase 3

Tanaka

Muto

Shima

et al. 2016

Journal of Biological Chemistry

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“…Interestingly, Rif1 is known to interact with Sirt3, Sirt7 (40), and Setdb1 (41,42). Sirt3 and Sirt7 deacetylate histones, whereas Setdb1 methylates histone at H3-K9.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Regulation of the Blimp-1 Gene (Prdm1) in B Cells Involves Bach2 and Histone Deacetylase 3

Tanaka

Muto

Shima

et al. 2016

Journal of Biological Chemistry

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“…Activation of Zscan4 in ESCs is associated with rapid telomere extension by promoting T-SCE (Zalzman et al 2010;Dan et al 2014). Zscan4 is specifically expressed in 2Cs, and telomere elongation takes place most dramatically at the 2C stage through a T-SCE-based mechanism (Liu et al 2007).…”

Section: Role Of Tet Proteins In Repeat Silencing and Telomere Regulamentioning

confidence: 99%

Role of Tet proteins in enhancer activity and telomere elongation

et al. 2014

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DNA methylation at the C-5 position of cytosine (5mC) is one of the best-studied epigenetic modifications and plays important roles in diverse biological processes. Iterative oxidation of 5mC by the ten-eleven translocation (Tet) family of proteins generates 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). 5fC and 5caC are selectively recognized and excised by thymine DNA glycosylase (TDG), leading to DNA demethylation. Functional characterization of Tet proteins has been complicated by the redundancy between the three family members. Using CRISPR/Cas9 technology, we generated mouse embryonic stem cells (ESCs) deficient for all three Tet proteins (Tet triple knockout [TKO]). Whole-genome bisulfite sequencing (WGBS) analysis revealed that Tet-mediated DNA demethylation mainly occurs at distally located enhancers and fine-tunes the transcription of genes associated with these regions. Functional characterization of Tet TKO ESCs revealed a role for Tet proteins in regulating the twocell embryo (2C)-like state under ESC culture conditions. In addition, Tet TKO ESCs exhibited increased telomeresister chromatid exchange and elongated telomeres. Collectively, our study reveals a role for Tet proteins in not only DNA demethylation at enhancers but also regulating the 2C-like state and telomere homeostasis.

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“…One study claimed that NHEJ repair mechanism is observed very frequently in pancreatic cancer and another study showed that RIF1 gene increases the efficiency of NHEJ repair mechanism [3,4]. The next step to elucidate the role of RIF1 gene could be to use siRNA's to silence the gene as and then observe the effect in pancreatic cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…High expression levels of RIF1 are associated with transformation in ESC's [3]. RIF1 also promotes NHEJ in stem cells; thus, it avoids chemotherapy in cancer stem cells [4].…”

mentioning

confidence: 99%

Investigation of the expression of RIF1 gene on head and neck, pancreatic and brain cancer and cancer stem cells

GursesCila¹,

Acar²,

Barut³

et al. 2016

CIM

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Investigation of the expression of RIF1 gene on head and neck, pancreatic and brain cancer and cancer stem cells Abstract Purpose: Recent studies have shown that cancer stem cells are resistant to chemotherapy. The aim of this study was to compare RIF1 gene expression in head and neck, pancreatic cancer and glioma cell lines and the cancer stem cells isolated from these cell lines.Methods: UT-SCC-74 from Turku University and UT-SCC-74B primary tumor metastasis and neck cancer cell lines, YKG-1 glioma cancer cell line from RIKEN, pancreatic cancer cell lines and ASPC-1 cells from ATCC were grown in cell culture. To isolate cancer stem cells, ALDH-1 for UT-SCC-74 and UT-SCC-74B cell line, CD-133 for YKG-1 cell line and CD-24 for ASPC-1 cell line, were used as markers of cancer stem cells. RNA isolation was performed for both cancer lines and cancer stem cells. RNAs were converted to cDNA. RIF1 gene expression was performed by qRT-PCR analysis. RIF1 gene expression was compared with cancer cell lines and cancer stem cells isolated from these cell lines. The possible effect of RIF1 gene was evaluated.Results: In the pancreatic cells, RIF1 gene expression in the stem cell-positive cell line was 256 time that seen in the stem cell-negative cell line. Conclusion:Considering the importance of RIF1 in NHEJ and of NHEJ in pancreatic cancer, RIF1 may be one of the genes that plays an important role in the diagnoses and therapeutic treatment of pancreatic cancer. The results of head and neck and brain cancers are inconclusive and further studies are required to elucidate the connection between RIF1 gene and these other types of cancers.SUPPLEMENT

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Rif1 Maintains Telomere Length Homeostasis of ESCs by Mediating Heterochromatin Silencing

Cited by 117 publications

References 57 publications

Epigenetic Regulation of the Blimp-1 Gene (Prdm1) in B Cells Involves Bach2 and Histone Deacetylase 3

Epigenetic Regulation of the Blimp-1 Gene (Prdm1) in B Cells Involves Bach2 and Histone Deacetylase 3

Role of Tet proteins in enhancer activity and telomere elongation

Investigation of the expression of RIF1 gene on head and neck, pancreatic and brain cancer and cancer stem cells

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