TY - JOUR
T1 - Transcription regulation of CDKN1A (p21/CIP1/WAF1) by TRF2 is epigenetically controlled through the REST repressor complex
AU - Hussain, Tabish
AU - Saha, Dhurjhoti
AU - Purohit, Gunjan
AU - Kar, Anirban
AU - Kishore Mukherjee, Anand
AU - Sharma, Shalu
AU - Sengupta, Suman
AU - Dhapola, Parashar
AU - Maji, Basudeb
AU - Vedagopuram, Sreekanth
AU - Horikoshi, Nobuko T.
AU - Horikoshi, Nobuo
AU - Pandita, Raj K.
AU - Bhattacharya, Santanu
AU - Bajaj, Avinash
AU - Riou, Jean François
AU - Pandita, Tej K.
AU - Chowdhury, Shantanu
N1 - Funding Information:
This work was supported by Wellcome Trust/Department of Biotechnology (DBT) India Alliance Grant 500127/Z/09/Z (to S. C.). Research fellowship support from Wellcome Trust/DBT India Alliance (DS, SuS, AK, SaS), Council of Scientific and Industrial Research (TH, GP, PD) and research funding from CSIR (GENCODE) is acknowledged. NIH RO1: CA129537 and GM109768 grant to RKP and TKP are acknowledged. We thank Jean-Francois Riou for providing the library of G4-specific ligands as a gift. We thank S. Neidle, S. Balasubramanian, the M. P. Teulade-Fichou laboratory, Nagasawa K and Patrick Mailliet for G4 ligands used in this study.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - We observed extra-telomeric binding of the telomere repeat binding factor TRF2 within the promoter of the cyclin-dependent kinase CDKNIA (p21/CIP1/WAF1). This result in TRF2 induced transcription repression of p21. Interestingly, p21 repression was through engagement of the REST-coREST-LSD1-repressor complex and altered histone marks at the p21 promoter in a TRF2-dependent fashion. Furthermore, mutational analysis shows p21 repression requires interaction of TRF2 with a p21 promoter G-quadruplex. Physiologically, TRF2-mediated p21 repression attenuated drug-induced activation of cellular DNA damage response by evading G2/M arrest in cancer cells. Together these reveal for the first time role of TRF2 in REST-repressor complex mediated transcription repression.
AB - We observed extra-telomeric binding of the telomere repeat binding factor TRF2 within the promoter of the cyclin-dependent kinase CDKNIA (p21/CIP1/WAF1). This result in TRF2 induced transcription repression of p21. Interestingly, p21 repression was through engagement of the REST-coREST-LSD1-repressor complex and altered histone marks at the p21 promoter in a TRF2-dependent fashion. Furthermore, mutational analysis shows p21 repression requires interaction of TRF2 with a p21 promoter G-quadruplex. Physiologically, TRF2-mediated p21 repression attenuated drug-induced activation of cellular DNA damage response by evading G2/M arrest in cancer cells. Together these reveal for the first time role of TRF2 in REST-repressor complex mediated transcription repression.
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U2 - 10.1038/s41598-017-11177-1
DO - 10.1038/s41598-017-11177-1
M3 - Article
C2 - 28912501
AN - SCOPUS:85029488517
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 11541
ER -