Mutation of the TERT promoter, switch to active chromatin, and monoallelic TERT expression in multiple cancers
Somatic mutations in the promoter of the gene for telomerase reverse transcriptase (TERT) are the most common noncoding mutations in cancer. They are thought to activate telomerase, contributing to proliferative immortality, but the molecular events driving TERT activation are largely unknown. We ob...
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| Veröffentlicht in: | Genes & development 2015-11, Vol.29 (21), p.2219-2224 |
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| creator | Stern, Josh Lewis Theodorescu, Dan Vogelstein, Bert Papadopoulos, Nickolas Cech, Thomas R |
| description | Somatic mutations in the promoter of the gene for telomerase reverse transcriptase (TERT) are the most common noncoding mutations in cancer. They are thought to activate telomerase, contributing to proliferative immortality, but the molecular events driving TERT activation are largely unknown. We observed in multiple cancer cell lines that mutant TERT promoters exhibit the H3K4me2/3 mark of active chromatin and recruit the GABPA/B1 transcription factor, while the wild-type allele retains the H3K27me3 mark of epigenetic silencing; only the mutant promoters are transcriptionally active. These results suggest how a single-base-pair mutation can cause a dramatic epigenetic switch and monoallelic expression. |
| doi_str_mv | 10.1101/gad.269498.115 |
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They are thought to activate telomerase, contributing to proliferative immortality, but the molecular events driving TERT activation are largely unknown. We observed in multiple cancer cell lines that mutant TERT promoters exhibit the H3K4me2/3 mark of active chromatin and recruit the GABPA/B1 transcription factor, while the wild-type allele retains the H3K27me3 mark of epigenetic silencing; only the mutant promoters are transcriptionally active. These results suggest how a single-base-pair mutation can cause a dramatic epigenetic switch and monoallelic expression.</description><subject>Cell Line, Tumor</subject><subject>Chromatin - genetics</subject><subject>Chromatin - metabolism</subject><subject>Epigenesis, Genetic - genetics</subject><subject>GA-Binding Protein Transcription Factor - genetics</subject><subject>GA-Binding Protein Transcription Factor - metabolism</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene Silencing</subject><subject>Humans</subject><subject>Mutation - genetics</subject><subject>Neoplasms - genetics</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Protein Binding</subject><subject>Research Communication</subject><subject>Telomerase - genetics</subject><issn>0890-9369</issn><issn>1549-5477</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUUtr3DAYFKUh2aa59lh07CHeSJb1uhRKSNpCSiBsz0KW5ayKLDmSnMe_r5ZNQ3rL6WP4ZoYZBoBPGK0xRvjsVg_rlslOiorpO7DCtJMN7Th_D1ZISNRIwuQR-JDzH4QQQ4wdgqOWUUwrfwXCr6Xo4mKAcYRla-Hm4mYD5xSnWGw6hfnBFbOFJUJtiru30GzrryrCKdRhgFMMUXtvvTN7qX2ck8155-gCnBZf3OyrTAdjU_4IDkbtsz15vsfg9-XF5vxHc3X9_ef5t6vGdEKWhuJxEIyNUmJhsURUjj3CDIue8V7jruWD6UYhCO250BwPsq0tB66RJshyTY7B173vvPSTHYwNJWmv5uQmnZ5U1E79_wluq27jvepYxyml1eDLs0GKd4vNRU0uG-u9DjYuWWHOiSCkRnkDlWAu2lqlUtd7qkkx52THl0QYqd2equ6p9ntWvIvx-XWPF_q_Aclf3vqcpw</recordid><startdate>20151101</startdate><enddate>20151101</enddate><creator>Stern, Josh Lewis</creator><creator>Theodorescu, Dan</creator><creator>Vogelstein, Bert</creator><creator>Papadopoulos, Nickolas</creator><creator>Cech, Thomas R</creator><general>Cold Spring Harbor Laboratory Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20151101</creationdate><title>Mutation of the TERT promoter, switch to active chromatin, and monoallelic TERT expression in multiple cancers</title><author>Stern, Josh Lewis ; 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| subjects | Cell Line, Tumor Chromatin - genetics Chromatin - metabolism Epigenesis, Genetic - genetics GA-Binding Protein Transcription Factor - genetics GA-Binding Protein Transcription Factor - metabolism Gene Expression Regulation, Neoplastic Gene Silencing Humans Mutation - genetics Neoplasms - genetics Promoter Regions, Genetic - genetics Protein Binding Research Communication Telomerase - genetics |
| title | Mutation of the TERT promoter, switch to active chromatin, and monoallelic TERT expression in multiple cancers |
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