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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Detalhes bibliográficos
Autores: Berdasco, María, Gómez, Antonio, Rubio, Marcos J, Català-Mora, Jaume, Zanón-Moreno, Vicente, Lopez, Miguel, Hernández, Cristina, Yoshida, Shigeo, Nakama, Takahito, Ishikawa, Keijiro, Ishibashi, Tatsuro, Boubekeur, Amina M, Louhibi, Lotfi, Pujana, Miguel Angel, Sayols, Sergi, Setien, Fernando, Corella, Dolores, de Torres, Carmen, Parareda, Andreu, Mora, Jaume, Zhao, Ling, Zhang, Kang, Lleonart, Matilde E, Alonso, Javier, Simó, Rafael, Caminal, Josep M, Esteller, Manel
Tipo de documento: artigo
Data de publicação:2017
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositório:Repisalud
Idioma:inglês
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/9150
Acesso em linha:http://hdl.handle.net/20.500.12105/9150
Access Level:Acceso aberto
Palavra-chave:Adult
Child
Child, Preschool
Eye Neoplasms
Female
Humans
Male
DNA Methylation
DNA, Neoplasm
Diabetic Retinopathy
Epigenesis, Genetic
Eye
Eye Proteins
Gene Expression Regulation, Neoplastic
MAP Kinase Signaling System
Neoplasm Proteins
Retinal Neovascularization
Descrição
Resumo: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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