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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...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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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. |
format | Online Article Text |
id | pubmed-5599563 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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