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

Hussain, Tabish and Saha, Dhurjhoti and Purohit, Gunjan and Kar, Anirban and Mukherjee, Anand Kishore and Sharma, Shalu and Sengupta, Suman and Dhapola, Parashar and Maji, Basudeb and Vedagopuram, Sreekanth and Horikoshi, Nobuko T and Horikoshi, Nobuo and Pandita, Raj K and Bhattacharya, Santanu and Bajaj, Avinash and Riou, Jean-Francois and Pandita, Tej K and Chowdhury, Shantanu (2017) Transcription regulation of CDKN1A (p21/CIP1/WAF1) by TRF2 is epigenetically controlled through the REST repressor complex. In: SCIENTIFIC REPORTS, 7 .

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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.

Item Type:	Journal Article
Publication:	SCIENTIFIC REPORTS
Additional Information:	Copy right for this article belongs to the NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
Department/Centre:	Division of Chemical Sciences > Organic Chemistry
Date Deposited:	07 Oct 2017 06:07
Last Modified:	07 Oct 2017 06:07
URI:	http://eprints.iisc.ac.in/id/eprint/57974

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