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5-Hydroxymethylcytosine Plays a Critical Role in Glioblastomagenesis by Recruiting the CHTOP-Methylosome Complex
- Source :
- Cell Reports, Vol 9, Iss 1, Pp 48-60 (2014)
- Publisher :
- The Authors. Published by Elsevier Inc.
-
Abstract
- 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.
- Subjects :
- Protein-Arginine N-Methyltransferases
Transcription, Genetic
Carcinogenesis
Methylation
General Biochemistry, Genetics and Molecular Biology
Mixed Function Oxygenases
Histones
Histone H4
Cytosine
chemistry.chemical_compound
Transcription (biology)
Proto-Oncogene Proteins
Humans
Epigenetics
lcsh:QH301-705.5
Methylosome
5-Hydroxymethylcytosine
Genetics
biology
Brain Neoplasms
Nuclear Proteins
Acetylation
Chromatin
Cell biology
DNA-Binding Proteins
Gene Expression Regulation, Neoplastic
Repressor Proteins
HEK293 Cells
chemistry
lcsh:Biology (General)
5-Methylcytosine
biology.protein
Cyclin-dependent kinase 6
Glioblastoma
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 22111247
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Cell Reports
- Accession number :
- edsair.doi.dedup.....0b103a3366b6fa46a3d6524ffb158dcb
- Full Text :
- https://doi.org/10.1016/j.celrep.2014.08.071