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

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-represso...

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Detalles Bibliográficos
Autores principales: Hussain, Tabish, Saha, Dhurjhoti, Purohit, Gunjan, Kar, Anirban, Kishore Mukherjee, Anand, Sharma, Shalu, Sengupta, Suman, Dhapola, Parashar, Maji, Basudeb, Vedagopuram, Sreekanth, Horikoshi, Nobuko T., Horikoshi, Nobuo, Pandita, Raj K., Bhattacharya, Santanu, Bajaj, Avinash, Riou, Jean-François, Pandita, Tej K., Chowdhury, Shantanu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5599563/
https://www.ncbi.nlm.nih.gov/pubmed/28912501
http://dx.doi.org/10.1038/s41598-017-11177-1
Descripción
Sumario: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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