| Literature DB >> 29878202 |
Agustin F Fernandez1, Gustavo F Bayón1, Marta I Sierra1, Rocio G Urdinguio2, Estela G Toraño1,2, Maria G García1,2, Antonella Carella1,2, Virginia López2, Pablo Santamarina1,2, Raúl F Pérez1,2, Thalía Belmonte1,2, Juan Ramon Tejedor1, Isabel Cobo1,3, Pablo Menendez3,4, Cristina Mangas1, Cecilia Ferrero1, Luis Rodrigo5, Aurora Astudillo6, Ignacio Ortea7, Sergio Cueto Díaz8, Pablo Rodríguez-Gonzalez9, J Ignacio García Alonso9, Manuela Mollejo10, Bárbara Meléndez10, Gemma Domínguez11, Felix Bonilla11, Mario F Fraga2.
Abstract
Aberrant DNA hypermethylation is a hallmark of cancer although the underlying molecular mechanisms are still poorly understood. To study the possible role of 5-hydroxymethylcytosine (5hmC) in this process we analyzed the global and locus-specific genome-wide levels of 5hmC and 5-methylcytosine (5mC) in human primary samples from 12 non-tumoral brains and 53 gliomas. We found that the levels of 5hmC identified in non-tumoral samples were significantly reduced in gliomas. Strikingly, hypo-hydroxymethylation at 4627 (9.3%) CpG sites was associated with aberrant DNA hypermethylation and was strongly enriched in CpG island shores. The DNA regions containing these CpG sites were enriched in H3K4me2 and presented a different genuine chromatin signature to that characteristic of the genes classically aberrantly hypermethylated in cancer. As this 5mC gain is inversely correlated with loss of 5hmC and has not been identified with classical sodium bisulfite-based technologies, we conclude that our data identifies a novel 5hmC-dependent type of aberrant DNA hypermethylation in glioma.Entities:
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Year: 2018 PMID： 29878202 DOI： 10.1093/hmg/ddy214
Source DB: PubMed Journal: Hum Mol Genet ISSN： 0964-6906 Impact factor: 6.150