| Literature DB >> 25284789 |
Hiroki Takai1, Koji Masuda2, Tomohiro Sato1, Yuriko Sakaguchi3, Takeo Suzuki3, Tsutomu Suzuki3, Ryo Koyama-Nasu1, Yukiko Nasu-Nishimura1, Yuki Katou2, Haruo Ogawa4, Yasuyuki Morishita5, Hiroko Kozuka-Hata6, Masaaki Oyama6, Tomoki Todo7, Yasushi Ino7, Akitake Mukasa7, Nobuhito Saito7, Chikashi Toyoshima4, Katsuhiko Shirahige2, Tetsu Akiyama8.
Abstract
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.Entities:
Mesh：
Substances：
Year: 2014 PMID： 25284789 DOI： 10.1016/j.celrep.2014.08.071
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423