DNA Methylomes Reveal Biological Networks Involved in Human Eye Development, Functions and Associated Disorders View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

María Berdasco, Antonio Gómez, Marcos J. Rubio, Jaume Català-Mora, Vicente Zanón-Moreno, Miguel Lopez, Cristina Hernández, Shigeo Yoshida, Takahito Nakama, Keijiro Ishikawa, Tatsuro Ishibashi, Amina M. Boubekeur, Lotfi Louhibi, Miguel A Pujana, Sergi Sayols, Fernando Setien, Dolores Corella, Carmen de Torres, Andreu Parareda, Jaume Mora, Ling Zhao, Kang Zhang, Matilde E. Lleonart, Javier Alonso, Rafael Simó, Josep M. Caminal, Manel Esteller

ABSTRACT

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. More... »

PAGES

11762

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-017-12084-1

DOI

http://dx.doi.org/10.1038/s41598-017-12084-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1091675745

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28924151


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