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

Meng Hsun Hsieh, Yi Ting Chen, You Tzung Chen, Yi Hsuan Lee, Jean Lu, Chung Liang Chien, Hsin Fu Chen, Hong Nerng Ho, Chia Jung Yu, Zhao Qi Wang, Shu Chun Teng

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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 Krüppel-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(ADP-ribose) 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(ADP-ribose) polymerase activity is dispensable, while the oligo(ADP-ribose) polymerase activity is required for the PARP1- and KLF4-mediated TERTactivation. 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.

Original languageEnglish
Pages (from-to)10492-10503
Number of pages12
JournalNucleic Acids Research
Volume45
Issue number18
DOIs
Publication statusPublished - Oct 1 2017
Externally publishedYes

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Neoplastic Stem Cells
Telomerase
Transcription Factors
Embryonic Stem Cells
Poly(ADP-ribose) Polymerases
Poly (ADP-Ribose) Polymerase-1
Differentiation Antigens
Neoplasms
Stem Cells
Genome

ASJC Scopus subject areas

  • Genetics

Cite this

Hsieh, M. H., Chen, Y. T., Chen, Y. T., Lee, Y. H., Lu, J., Chien, C. L., ... Teng, S. C. (2017). PARP1 controls KLF4-mediated telomerase expression in stem cells and cancer cells. Nucleic Acids Research, 45(18), 10492-10503. https://doi.org/10.1093/nar/gkx683

PARP1 controls KLF4-mediated telomerase expression in stem cells and cancer cells. / Hsieh, Meng Hsun; Chen, Yi Ting; Chen, You Tzung; Lee, Yi Hsuan; Lu, Jean; Chien, Chung Liang; Chen, Hsin Fu; Ho, Hong Nerng; Yu, Chia Jung; Wang, Zhao Qi; Teng, Shu Chun.

In: Nucleic Acids Research, Vol. 45, No. 18, 01.10.2017, p. 10492-10503.

Research output: Contribution to journalArticle

Hsieh, MH, Chen, YT, Chen, YT, Lee, YH, Lu, J, Chien, CL, Chen, HF, Ho, HN, Yu, CJ, Wang, ZQ & Teng, SC 2017, 'PARP1 controls KLF4-mediated telomerase expression in stem cells and cancer cells', Nucleic Acids Research, vol. 45, no. 18, pp. 10492-10503. https://doi.org/10.1093/nar/gkx683
Hsieh MH, Chen YT, Chen YT, Lee YH, Lu J, Chien CL et al. PARP1 controls KLF4-mediated telomerase expression in stem cells and cancer cells. Nucleic Acids Research. 2017 Oct 1;45(18):10492-10503. https://doi.org/10.1093/nar/gkx683
Hsieh, Meng Hsun ; Chen, Yi Ting ; Chen, You Tzung ; Lee, Yi Hsuan ; Lu, Jean ; Chien, Chung Liang ; Chen, Hsin Fu ; Ho, Hong Nerng ; Yu, Chia Jung ; Wang, Zhao Qi ; Teng, Shu Chun. / PARP1 controls KLF4-mediated telomerase expression in stem cells and cancer cells. In: Nucleic Acids Research. 2017 ; Vol. 45, No. 18. pp. 10492-10503.
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