RRC ID 67667
Author Takai H, Masuda K, Sato T, Sakaguchi Y, Suzuki T, Suzuki T, Koyama-Nasu R, Nasu-Nishimura Y, Katou Y, Ogawa H, Morishita Y, Kozuka-Hata H, Oyama M, Todo T, Ino Y, Mukasa A, Saito N, Toyoshima C, Shirahige K, Akiyama T.
Title 5-Hydroxymethylcytosine plays a critical role in glioblastomagenesis by recruiting the CHTOP-methylosome complex.
Journal Cell Rep
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.
Volume 9(1)
Pages 48-60
Published 2014-10-9
DOI 10.1016/j.celrep.2014.08.071
PII S2211-1247(14)00763-3
PMID 25284789
MeSH 5-Methylcytosine / analogs & derivatives Acetylation Brain Neoplasms / genetics Brain Neoplasms / metabolism* Carcinogenesis / genetics Carcinogenesis / metabolism* Chromatin / genetics Chromatin / metabolism Cytosine / analogs & derivatives* Cytosine / biosynthesis Cytosine / metabolism DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Gene Expression Regulation, Neoplastic Glioblastoma / genetics Glioblastoma / metabolism* HEK293 Cells Histones / genetics Histones / metabolism Humans Methylation Mixed Function Oxygenases Nuclear Proteins / genetics Nuclear Proteins / metabolism Protein-Arginine N-Methyltransferases / genetics Protein-Arginine N-Methyltransferases / metabolism Proto-Oncogene Proteins / genetics Proto-Oncogene Proteins / metabolism Repressor Proteins / genetics Repressor Proteins / metabolism Transcription Factors / genetics Transcription Factors / metabolism Transcription, Genetic
IF 8.109
DNA material pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393) CS-RfA-CG (RDB04390) pENTR4-H1 (RDB04395)