5-Hydroxymethylcytosine Plays a Critical Role in Glioblastomagenesis by Recruiting the CHTOP-Methylosome Complex
Summary: The development of cancer is driven not only by genetic mutations but also by epigenetic alterations. Here, we show that TET1-mediated production of 5-hydroxymethylcytosine (5hmC) is required for the tumorigenicity of glioblastoma cells. Furthermore, we demonstrate that chromatin target of...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-10-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124714007633 |
| _version_ | 1811225057593131008 |
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| author | Hiroki Takai Koji Masuda Tomohiro Sato Yuriko Sakaguchi Takeo Suzuki Tsutomu Suzuki Ryo Koyama-Nasu Yukiko Nasu-Nishimura Yuki Katou Haruo Ogawa Yasuyuki Morishita Hiroko Kozuka-Hata Masaaki Oyama Tomoki Todo Yasushi Ino Akitake Mukasa Nobuhito Saito Chikashi Toyoshima Katsuhiko Shirahige Tetsu Akiyama |
| author_facet | Hiroki Takai Koji Masuda Tomohiro Sato Yuriko Sakaguchi Takeo Suzuki Tsutomu Suzuki Ryo Koyama-Nasu Yukiko Nasu-Nishimura Yuki Katou Haruo Ogawa Yasuyuki Morishita Hiroko Kozuka-Hata Masaaki Oyama Tomoki Todo Yasushi Ino Akitake Mukasa Nobuhito Saito Chikashi Toyoshima Katsuhiko Shirahige Tetsu Akiyama |
| author_sort | Hiroki Takai |
| collection | DOAJ |
| description | Summary: The development of cancer is driven not only by genetic mutations but also by epigenetic alterations. Here, we show that TET1-mediated production of 5-hydroxymethylcytosine (5hmC) is required for the tumorigenicity of glioblastoma cells. Furthermore, we demonstrate that chromatin target of PRMT1 (CHTOP) binds to 5hmC. We found that CHTOP is associated with an arginine methyltransferase complex, termed the methylosome, and that this promotes the PRMT1-mediated methylation of arginine 3 of histone H4 (H4R3) in genes involved in glioblastomagenesis, including EGFR, AKT3, CDK6, CCND2, and BRAF. Moreover, we found that CHTOP and PRMT1 are essential for the expression of these genes and that CHTOP is required for the tumorigenicity of glioblastoma cells. These results suggest that 5hmC plays a critical role in glioblastomagenesis by recruiting the CHTOP-methylosome complex to selective sites on the chromosome, where it methylates H4R3 and activates the transcription of cancer-related genes. : The development of cancer is driven not only by genetic mutations but also by chromatin and DNA modification changes. Takai et al. now show that proneural glioblastomas contain high levels of 5hmC and TET1. Production of 5hmC is required for the tumorigenicity of glioblastoma cells. Furthermore, 5hmC recruits the CHTOP-methylosome complex to selective sites on the chromosome, where it methylates H4R3 and activates the transcription of cancer-related genes. |
| first_indexed | 2024-04-12T09:00:42Z |
| format | Article |
| id | doaj.art-6e167373836c4249903547f389fae70e |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-12T09:00:42Z |
| publishDate | 2014-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-6e167373836c4249903547f389fae70e2022-12-22T03:39:15ZengElsevierCell Reports2211-12472014-10-019148605-Hydroxymethylcytosine Plays a Critical Role in Glioblastomagenesis by Recruiting the CHTOP-Methylosome ComplexHiroki Takai0Koji Masuda1Tomohiro Sato2Yuriko Sakaguchi3Takeo Suzuki4Tsutomu Suzuki5Ryo Koyama-Nasu6Yukiko Nasu-Nishimura7Yuki Katou8Haruo Ogawa9Yasuyuki Morishita10Hiroko Kozuka-Hata11Masaaki Oyama12Tomoki Todo13Yasushi Ino14Akitake Mukasa15Nobuhito Saito16Chikashi Toyoshima17Katsuhiko Shirahige18Tetsu Akiyama19Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, JapanLaboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, JapanLaboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, JapanDepartment of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656, JapanDepartment of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656, JapanDepartment of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656, JapanLaboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, JapanLaboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, JapanLaboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, JapanLaboratory of Membrane Proteins, Center for Structural Biology of Challenging Proteins, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, JapanDepartment of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, JapanMedical Proteomics Laboratory, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, JapanMedical Proteomics Laboratory, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, JapanDepartment of Neurosurgery, The University of Tokyo Hospital, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, JapanDepartment of Neurosurgery, The University of Tokyo Hospital, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, JapanDepartment of Neurosurgery, The University of Tokyo Hospital, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, JapanDepartment of Neurosurgery, The University of Tokyo Hospital, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, JapanLaboratory of Membrane Proteins, Center for Structural Biology of Challenging Proteins, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, JapanLaboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, JapanLaboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan; Corresponding authorSummary: The development of cancer is driven not only by genetic mutations but also by epigenetic alterations. Here, we show that TET1-mediated production of 5-hydroxymethylcytosine (5hmC) is required for the tumorigenicity of glioblastoma cells. Furthermore, we demonstrate that chromatin target of PRMT1 (CHTOP) binds to 5hmC. We found that CHTOP is associated with an arginine methyltransferase complex, termed the methylosome, and that this promotes the PRMT1-mediated methylation of arginine 3 of histone H4 (H4R3) in genes involved in glioblastomagenesis, including EGFR, AKT3, CDK6, CCND2, and BRAF. Moreover, we found that CHTOP and PRMT1 are essential for the expression of these genes and that CHTOP is required for the tumorigenicity of glioblastoma cells. These results suggest that 5hmC plays a critical role in glioblastomagenesis by recruiting the CHTOP-methylosome complex to selective sites on the chromosome, where it methylates H4R3 and activates the transcription of cancer-related genes. : The development of cancer is driven not only by genetic mutations but also by chromatin and DNA modification changes. Takai et al. now show that proneural glioblastomas contain high levels of 5hmC and TET1. Production of 5hmC is required for the tumorigenicity of glioblastoma cells. Furthermore, 5hmC recruits the CHTOP-methylosome complex to selective sites on the chromosome, where it methylates H4R3 and activates the transcription of cancer-related genes.http://www.sciencedirect.com/science/article/pii/S2211124714007633 |
| spellingShingle | Hiroki Takai Koji Masuda Tomohiro Sato Yuriko Sakaguchi Takeo Suzuki Tsutomu Suzuki Ryo Koyama-Nasu Yukiko Nasu-Nishimura Yuki Katou Haruo Ogawa Yasuyuki Morishita Hiroko Kozuka-Hata Masaaki Oyama Tomoki Todo Yasushi Ino Akitake Mukasa Nobuhito Saito Chikashi Toyoshima Katsuhiko Shirahige Tetsu Akiyama 5-Hydroxymethylcytosine Plays a Critical Role in Glioblastomagenesis by Recruiting the CHTOP-Methylosome Complex Cell Reports |
| title | 5-Hydroxymethylcytosine Plays a Critical Role in Glioblastomagenesis by Recruiting the CHTOP-Methylosome Complex |
| title_full | 5-Hydroxymethylcytosine Plays a Critical Role in Glioblastomagenesis by Recruiting the CHTOP-Methylosome Complex |
| title_fullStr | 5-Hydroxymethylcytosine Plays a Critical Role in Glioblastomagenesis by Recruiting the CHTOP-Methylosome Complex |
| title_full_unstemmed | 5-Hydroxymethylcytosine Plays a Critical Role in Glioblastomagenesis by Recruiting the CHTOP-Methylosome Complex |
| title_short | 5-Hydroxymethylcytosine Plays a Critical Role in Glioblastomagenesis by Recruiting the CHTOP-Methylosome Complex |
| title_sort | 5 hydroxymethylcytosine plays a critical role in glioblastomagenesis by recruiting the chtop methylosome complex |
| url | http://www.sciencedirect.com/science/article/pii/S2211124714007633 |
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