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Sci Rep. 2017 Sep 14;7(1):11541. doi: 10.1038/s41598-017-11177-1.

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

Author information

1
Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, Mathura Road, New Delhi, 110025, India.
2
Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Genomics and Integrative Biology, Mathura Road, New Delhi, 110025, India.
3
G.N.R. Knowledge Centre for Genome Informatics, CSIR- Institute of Genomics and Integrative Biology, Mathura Road, New Delhi, 110025, India.
4
Department of Organic Chemistry, Indian Institute of Science, Bangalore, India.
5
Chemical Biology Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, 560012, India.
6
Laboratory of Nanotechnology and Chemical Biology, Regional Centre for Biotechnology, NCR Biotech Cluster, Faridabad, Haryana, 121001, India.
7
Department of Radiation Oncology, The Houston Methodist Research Institute, Houston, TX, 77030, USA.
8
Structure des Acides Nucléiques, Télomères et Evolution, Muséum National d'Histoire Naturelle, 43 rue Cuvier, 75231, Paris cedex 05, France.
9
Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, Mathura Road, New Delhi, 110025, India. shantanuc@igib.res.in.
10
G.N.R. Knowledge Centre for Genome Informatics, CSIR- Institute of Genomics and Integrative Biology, Mathura Road, New Delhi, 110025, India. shantanuc@igib.res.in.
11
Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Genomics and Integrative Biology, Mathura Road, New Delhi, 110025, India. shantanuc@igib.res.in.

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.

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