PARP1 controls KLF4-mediated telomerase expression in stem cells and cancer cells

被引：38
作者：
Hsieh, Meng-Hsun [1 ]
Chen, Yi-Ting [1 ]
Chen, You-Tzung [2 ]
Lee, Yi-Hsuan [3 ]
Lu, Jean [3 ]
Chien, Chung-Liang [4 ]
Chen, Hsin-Fu [2 ,5 ,6 ]
Ho, Hong-Nerng [2 ,5 ,6 ]
Yu, Chia-Jung [7 ,8 ]
Wang, Zhao-Qi [9 ]
Teng, Shu-Chun [1 ,10 ,11 ]
机构：
[1] Natl Taiwan Univ, Dept Microbiol, Coll Med, Taipei 100, Taiwan
[2] Natl Taiwan Univ, Grad Inst Med Genom & Prote, Coll Med, Taipei 100, Taiwan
[3] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan
[4] Natl Taiwan Univ, Coll Med, Anat & Cell Biol, Taipei 100, Taiwan
[5] Natl Taiwan Univ Hosp, Dept Obstet & Gynecol, Taipei 100, Taiwan
[6] Natl Taiwan Univ Hosp, Inst Internal Med, Taipei 100, Taiwan
[7] Chang Gung Univ, Coll Med, Dept Cell & Mol Biol, Taoyuan 333, Taiwan
[8] Chang Gung Mem Hosp, Dept Thorac Med, Taoyuan 333, Taiwan
[9] FLI, Leibniz Inst Aging, D-07745 Jena, Germany
[10] Natl Taiwan Univ, PhD Program Translat Med, Taipei 100, Taiwan
[11] Acad Sinica, Taipei 100, Taiwan
来源：
NUCLEIC ACIDS RESEARCH | 2017年 / 45卷 / 18期
关键词：
POLY(ADP-RIBOSE) POLYMERASE 1; SELF-RENEWAL; HUMAN FIBROBLASTS; ADP-RIBOSYLATION; BETA-CATENIN; DNA-DAMAGE; ES CELLS; DIFFERENTIATION; GENERATION; TRANSCRIPTION;
D O I：
10.1093/nar/gkx683
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Telomerase is highly expressed in cancer and embryonic stem cells (ESCs) and implicated in controlling genome integrity, cancer formation and stemness. Previous studies identified that Kruppel-like transcription factor 4 (KLF4) activates telomerase reverse transcriptase (TERT) expression and contributes to the maintenance of self-renewal in ESCs. However, little is known about how KLF4 regulates TERT expression. Here, we discover poly(ADPribose) polymerase 1 (PARP1) as a novel KLF4-interacting partner. Knockdown of PARP1 reduces TERT expression and telomerase activity not only in cancer cells, but also in human and mouse ESCs. Recruitment of KLF4 to TERT promoter is reduced in PARP1-suppressed cells. The poly(ADPribose) polymerase activity is dispensable, while the oligo(ADP-ribose) polymerase activity is required for the PARP1-and KLF4-mediated TERT activation. Repression of Parp1 in mouse ESCs decreases expression of pluripotent markers and induces differentiation. These results suggest that PARP1 recruits KLF4 to activate telomerase expression and stem cell pluripotency, indicating a positive regulatory role of the PARP1-KLF4 complex in telomerase expression in cancer and stem cells.
引用
收藏
页码：10492 / 10503
页数：12
相关论文
共 53 条
  • [1] Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients
    Agarwal, Suneet
    Loh, Yuin-Han
    McLoughlin, Erin M.
    Huang, Junjiu
    Park, In-Hyun
    Miller, Justine D.
    Huo, Hongguang
    Okuka, Maja
    dos Reis, Rosana Maria
    Loewer, Sabine
    Ng, Huck-Hui
    Keefe, David L.
    Goldman, Frederick D.
    Klingelhutz, Aloysius J.
    Liu, Lin
    Daley, George Q.
    [J]. NATURE, 2010, 464 (7286) : 292 - U176
  • [2] Klf4 and Klf5 differentially inhibit mesoderm and endoderm differentiation in embryonic stem cells
    Aksoy, Irene
    Giudice, Vincent
    Delahaye, Edwige
    Wianny, Florence
    Aubry, Maxime
    Mure, Magali
    Chen, Jiaxuan
    Jauch, Ralf
    Bogu, Gireesh K.
    Nolden, Tobias
    Himmelbauer, Heinz
    Xavier Doss, Michael
    Sachinidis, Agapios
    Schulz, Herbert
    Hummel, Oliver
    Martinelli, Paola
    Huebner, Norbert
    Stanton, Lawrence W.
    Real, Francisco X.
    Bourillot, Pierre-Yves
    Savatier, Pierre
    [J]. NATURE COMMUNICATIONS, 2014, 5
  • [3] ALTHAUS FR, 1992, J CELL SCI, V102, P663
  • [4] Generation of pluripotent stem cells from adult mouse liver and stomach cells
    Aoi, Takashi
    Yae, Kojiro
    Nakagawa, Masato
    Ichisaka, Tomoko
    Okita, Keisuke
    Takahashi, Kazutoshi
    Chiba, Tsutomu
    Yamanaka, Shinya
    [J]. SCIENCE, 2008, 321 (5889) : 699 - 702
  • [5] Overexpression of telomerase confers growth advantage, stress resistance, and enhanced differentiation of ESCs toward the hematopoietic lineage
    Armstrong, L
    Saretzki, G
    Peters, H
    Wappler, I
    Evans, J
    Hole, N
    von Zglinicki, T
    Lako, M
    [J]. STEM CELLS, 2005, 23 (04) : 516 - 529
  • [6] Telomere shortening and loss of self-renewal in dyskeratosis congenita induced pluripotent stem cells
    Batista, Luis F. Z.
    Pech, MatthewF.
    Zhong, Franklin L.
    Nguyen, Ha Nam
    Xie, Kathleen T.
    Zaug, Arthur J.
    Crary, Sharon M.
    Choi, Jinkuk
    Sebastiano, Vittorio
    Cherry, Athena
    Giri, Neelam
    Wernig, Marius
    Alter, Blanche P.
    Cech, Thomas R.
    Savage, Sharon A.
    Pera, Renee A. Reijo
    Artandi, Steven E.
    [J]. NATURE, 2011, 474 (7351) : 399 - +
  • [7] Derivation, characterization and differentiation of human embryonic stem cells: comparing serum-containing versus serum-free media and evidence of germ cell differentiation
    Chen, H. -F.
    Kuo, H. -C.
    Chien, C. -L.
    Shun, C. -T.
    Yao, Y. -L.
    Ip, P. -L.
    Chuang, C. -Y.
    Wang, C. -C.
    Yang, Y. -S.
    Ho, H-N.
    [J]. HUMAN REPRODUCTION, 2007, 22 (02) : 567 - 577
  • [8] MacroH2A1.1 and PARP-1 cooperate to regulate transcription by promoting CBP-mediated H2B acetylation
    Chen, Hongshan
    Ruiz, Penelope D.
    Novikov, Leonid
    Casill, Alyssa D.
    Park, Jong Woo
    Gamble, Matthew J.
    [J]. NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2014, 21 (11) : 981 - 989
  • [9] Poly(ADP-ribose) polymerase 1 regulates nuclear reprogramming and promotes iPSC generation without c-Myc
    Chiou, Shih-Hwa
    Jiang, Bo-Hwa
    Yu, Yung-Luen
    Chou, Shih-Jie
    Tsai, Ping-Hsing
    Chang, Wei-Chao
    Chen, Liang-Kung
    Chen, Li-Hsin
    Chien, Yueh
    Chiou, Guang-Yuh
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2013, 210 (01) : 85 - 98
  • [10] Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions
    D'Amours, D
    Desnoyers, S
    D'Silva, I
    Poirier, GG
    [J]. BIOCHEMICAL JOURNAL, 1999, 342 : 249 - 268
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