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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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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:
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
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author 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
author_facet 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
author_sort Hussain, Tabish
collection PubMed
description 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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spelling pubmed-55995632017-09-15 Transcription regulation of CDKN1A (p21/CIP1/WAF1) by TRF2 is epigenetically controlled through the REST repressor complex 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 Sci Rep Article 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. Nature Publishing Group UK 2017-09-14 /pmc/articles/PMC5599563/ /pubmed/28912501 http://dx.doi.org/10.1038/s41598-017-11177-1 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
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
Transcription regulation of CDKN1A (p21/CIP1/WAF1) by TRF2 is epigenetically controlled through the REST repressor complex
title Transcription regulation of CDKN1A (p21/CIP1/WAF1) by TRF2 is epigenetically controlled through the REST repressor complex
title_full Transcription regulation of CDKN1A (p21/CIP1/WAF1) by TRF2 is epigenetically controlled through the REST repressor complex
title_fullStr Transcription regulation of CDKN1A (p21/CIP1/WAF1) by TRF2 is epigenetically controlled through the REST repressor complex
title_full_unstemmed Transcription regulation of CDKN1A (p21/CIP1/WAF1) by TRF2 is epigenetically controlled through the REST repressor complex
title_short Transcription regulation of CDKN1A (p21/CIP1/WAF1) by TRF2 is epigenetically controlled through the REST repressor complex
title_sort transcription regulation of cdkn1a (p21/cip1/waf1) by trf2 is epigenetically controlled through the rest repressor complex
topic Article
url 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
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