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*

*Corresponding author for this work

Research output: Contribution to journalArticle

19 Scopus citations

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 languageEnglish (US)
Article number11541
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • General

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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), [11541]. https://doi.org/10.1038/s41598-017-11177-1