Transcription regulation of CDKN1A (p21/CIP1/WAF1) by TRF2 is epigenetically controlled through the REST repressor complex

Tabish Hussain; Dhurjhoti Saha; Gunjan Purohit; Anirban Kar; Anand Kishore Mukherjee; Shalu Sharma; Suman Sengupta; Parashar Dhapola; Basudeb Maji; Sreekanth Vedagopuram; Nobuko T. Horikoshi; Nobuo Horikoshi; Raj K. Pandita; Santanu Bhattacharya; Avinash Bajaj; Jean François Riou; Tej K. Pandita; Shantanu Chowdhury

doi:10.1038/s41598-017-11177-1

Transcription regulation of CDKN1A (p21/CIP1/WAF1) by TRF2 is epigenetically controlled through the REST repressor complex

Tabish Hussain, Dhurjhoti Saha, Gunjan Purohit, Anirban Kar, Anand Kishore Mukherjee, Shalu Sharma, Suman Sengupta, Parashar Dhapola, Basudeb Maji, Sreekanth Vedagopuram, Nobuko T. Horikoshi, Nobuo Horikoshi, Raj K. Pandita, Santanu Bhattacharya, Avinash Bajaj, Jean François Riou, Tej K. Pandita, Shantanu Chowdhury

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Abstract

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.

Original language	English (US)
Article number	11541
Journal	Scientific reports
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41598-017-11177-1
State	Published - Dec 1 2017
Externally published	Yes

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Hussain, T., Saha, D., Purohit, G., Kar, A., Kishore Mukherjee, A., Sharma, S., Sengupta, S., Dhapola, P., Maji, B., Vedagopuram, S., Horikoshi, N. T., Horikoshi, N., Pandita, R. K., Bhattacharya, S., Bajaj, A., Riou, J. F., Pandita, T. K., & Chowdhury, S. (2017). Transcription regulation of CDKN1A (p21/CIP1/WAF1) by TRF2 is epigenetically controlled through the REST repressor complex. Scientific reports, 7(1), Article 11541. https://doi.org/10.1038/s41598-017-11177-1

Hussain, T, Saha, D, Purohit, G, Kar, A, Kishore Mukherjee, A, Sharma, S, Sengupta, S, Dhapola, P, Maji, B, Vedagopuram, S, Horikoshi, NT, Horikoshi, N, Pandita, RK, Bhattacharya, S, Bajaj, A, Riou, JF, Pandita, TK & Chowdhury, S 2017, 'Transcription regulation of CDKN1A (p21/CIP1/WAF1) by TRF2 is epigenetically controlled through the REST repressor complex', Scientific reports, vol. 7, no. 1, 11541. https://doi.org/10.1038/s41598-017-11177-1

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title = "Transcription regulation of CDKN1A (p21/CIP1/WAF1) by TRF2 is epigenetically controlled through the REST repressor complex",

abstract = "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.",

author = "Tabish Hussain and Dhurjhoti Saha and Gunjan Purohit and Anirban Kar and {Kishore Mukherjee}, Anand and Shalu Sharma and Suman Sengupta and Parashar Dhapola and Basudeb Maji and Sreekanth Vedagopuram and Horikoshi, {Nobuko T.} and Nobuo Horikoshi and Pandita, {Raj K.} and Santanu Bhattacharya and Avinash Bajaj and Riou, {Jean Fran{\c c}ois} and Pandita, {Tej K.} and Shantanu Chowdhury",

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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

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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Transcription regulation of CDKN1A (p21/CIP1/WAF1) by TRF2 is epigenetically controlled through the REST repressor complex

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