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 Gagos; Andrew Xiao; Lin Liu

doi:10.1016/j.devcel.2014.03.004

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 journal › Article › peer-review

100 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 language	English (US)
Pages (from-to)	7-19
Number of pages	13
Journal	Developmental Cell
Volume	29
Issue number	1
DOIs	https://doi.org/10.1016/j.devcel.2014.03.004
State	Published - Apr 14 2014

All Science Journal Classification (ASJC) codes

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

Access to Document

10.1016/j.devcel.2014.03.004

Cite this

Dan, J., Liu, Y., Liu, N., Chiourea, M., Okuka, M., Wu, T., Ye, X., Mou, C., Wang, L., Wang, L., Yin, Y., Yuan, J., Zuo, B., Wang, F., Li, Z., Pan, X., Yin, Z., Chen, L., Keefe, D. L., ... Liu, L. (2014). Rif1 Maintains Telomere Length Homeostasis of ESCs by Mediating Heterochromatin Silencing. Developmental Cell, 29(1), 7-19. https://doi.org/10.1016/j.devcel.2014.03.004

@article{47c44ec74c33444f9be7ff399404c8c1,

title = "Rif1 Maintains Telomere Length Homeostasis of ESCs by Mediating Heterochromatin Silencing",

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.",

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

note = "Funding Information: We thank Minoru Ko for providing Zscan4 antibody, Christina Glytsou for help on CO-FISH, Xinglong Zhou for fluorescence-activated cell sorting (FACS), Peter Lansdorp for the TFL-TELO software, Zhe Liu for H3K9me3 antibody (Upstate, 07-442), Jun Zhou for pCMV-Tag2B and pSIREN-RetroQ vector, and Mark Bartlam for reading the manuscript. This work was supported by the 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 funding to S.G.; and a Howard Temin Award (K99/R00 NIH/NCI 5R00CA131560 to A.X.). ",

year = "2014",

month = apr,

day = "14",

doi = "10.1016/j.devcel.2014.03.004",

language = "English (US)",

volume = "29",

pages = "7--19",

journal = "Developmental Cell",

issn = "1534-5807",

publisher = "Cell Press",

number = "1",

}

Dan, J, Liu, Y, Liu, N, Chiourea, M, Okuka, M, Wu, T, Ye, X, Mou, C, Wang, L, Wang, L, Yin, Y, Yuan, J, Zuo, B, Wang, F, Li, Z, Pan, X, Yin, Z, Chen, L, Keefe, DL, Gagos, S, Xiao, A & Liu, L 2014, 'Rif1 Maintains Telomere Length Homeostasis of ESCs by Mediating Heterochromatin Silencing', Developmental Cell, vol. 29, no. 1, pp. 7-19. https://doi.org/10.1016/j.devcel.2014.03.004

TY - JOUR

T1 - Rif1 Maintains Telomere Length Homeostasis of ESCs by Mediating Heterochromatin Silencing

AU - Dan, Jiameng

AU - Liu, Yifei

AU - Liu, Na

AU - Chiourea, Maria

AU - Okuka, Maja

AU - Wu, Tao

AU - Ye, Xiaoying

AU - Mou, Chunlin

AU - Wang, Lei

AU - Wang, Lingling

AU - Yin, Yu

AU - Yuan, Jihong

AU - Zuo, Bingfeng

AU - Wang, Fang

AU - Li, Zhiguo

AU - Pan, Xinghua

AU - Yin, Zhinan

AU - Chen, Lingyi

AU - Keefe, David L.

AU - Gagos, Sarantis

AU - Xiao, Andrew

AU - Liu, Lin

N1 - Funding Information: We thank Minoru Ko for providing Zscan4 antibody, Christina Glytsou for help on CO-FISH, Xinglong Zhou for fluorescence-activated cell sorting (FACS), Peter Lansdorp for the TFL-TELO software, Zhe Liu for H3K9me3 antibody (Upstate, 07-442), Jun Zhou for pCMV-Tag2B and pSIREN-RetroQ vector, and Mark Bartlam for reading the manuscript. This work was supported by the 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 funding to S.G.; and a Howard Temin Award (K99/R00 NIH/NCI 5R00CA131560 to A.X.).

PY - 2014/4/14

Y1 - 2014/4/14

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84898436514&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84898436514&partnerID=8YFLogxK

U2 - 10.1016/j.devcel.2014.03.004

DO - 10.1016/j.devcel.2014.03.004

M3 - Article

C2 - 24735877

AN - SCOPUS:84898436514

SN - 1534-5807

VL - 29

SP - 7

EP - 19

JO - Developmental Cell

JF - Developmental Cell

IS - 1

ER -

Rif1 Maintains Telomere Length Homeostasis of ESCs by Mediating Heterochromatin Silencing

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this