DNA methylomes reveal biological networks involved in human eye development, functions and associated disorders

This work provides a comprehensive CpG methylation landscape of the different layers of the human eye that unveils the gene networks associated with their biological functions and how these are disrupted in common visual disorders. Herein, we firstly determined the role of CpG methylation in the reg...

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Detalles Bibliográficos
Autores: Berdasco, María, Gómez, Antonio, Rubio, Marcos J., Català-Mora, Jaume, Zanón-Moreno, Vicente, Lopez, Miguel, Hernández-Munain, Cristina, Yoshida, Shigeo, Nakama, Takahito, Ishikawa, Keijiro, Ishibashi, Tatsuro, Boubekeur, Amina M., Louhibi, Lotfi, Pujana Genestar, M. Ángel, Sayols, Sergi, Setién, Fernando, Corella Piquer, Dolores, Torres Gómez-Pallete, Carmen de, Parareda Sallés, Andreu, Mora Graupera, Jaume, Zhao, Ling, Zhang, Kang, Lleonart, Matilde E., Alonso, Javier, Simó, Rafael, Caminal Mitjana, Josep Maria, Esteller, Manel, 1968-
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/122391
Acceso en línea:https://hdl.handle.net/2445/122391
Access Level:acceso abierto
Palabra clave:ADN
Metilació
Càncer
Oftalmologia
Ull
DNA
Methylation
Cancer
Ophthalmology
Eye
Descripción
Sumario:This work provides a comprehensive CpG methylation landscape of the different layers of the human eye that unveils the gene networks associated with their biological functions and how these are disrupted in common visual disorders. Herein, we firstly determined the role of CpG methylation in the regulation of ocular tissue-specification and described hypermethylation of retinal transcription factors (i.e., PAX6, RAX, SIX6) in a tissue-dependent manner. Second, we have characterized the DNA methylome of visual disorders linked to internal and external environmental factors. Main conclusions allow certifying that crucial pathways related to Wnt-MAPK signaling pathways or neuroinflammation are epigenetically controlled in the fibrotic disorders involved in retinal detachment, but results also reinforced the contribution of neurovascularization (ETS1, HES5, PRDM16) in diabetic retinopathy. Finally, we had studied the methylome in the most frequent intraocular tumors in adults and children (uveal melanoma and retinoblastoma, respectively). We observed that hypermethylation of tumor suppressor genes is a frequent event in ocular tumors, but also unmethylation is associated with tumorogenesis. Interestingly, unmethylation of the proto-oncogen RAB31 was a predictor of metastasis risk in uveal melanoma. Loss of methylation of the oncogenic mir-17-92 cluster was detected in primary tissues but also in blood from patients.

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