TY - JOUR
T1 - DNA Methylomes Reveal Biological Networks Involved in Human Eye Development, Functions and Associated Disorders
AU - Berdasco, María
AU - Gómez, Antonio
AU - Rubio, Marcos J.
AU - Català-Mora, Jaume
AU - Zanón-Moreno, Vicente
AU - Lopez, Miguel
AU - Hernández, Cristina
AU - Yoshida, Shigeo
AU - Nakama, Takahito
AU - Ishikawa, Keijiro
AU - Ishibashi, Tatsuro
AU - Boubekeur, Amina M.
AU - Louhibi, Lotfi
AU - Pujana, Miguel A.
AU - Sayols, Sergi
AU - Setien, Fernando
AU - Corella, Dolores
AU - De Torres, Carmen
AU - Parareda, Andreu
AU - Mora, Jaume
AU - Zhao, Ling
AU - Zhang, Kang
AU - Lleonart, Matilde E.
AU - Alonso, Javier
AU - Simó, Rafael
AU - Caminal, Josep M.
AU - Esteller, Manel
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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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U2 - 10.1038/s41598-017-12084-1
DO - 10.1038/s41598-017-12084-1
M3 - Article
C2 - 28924151
AN - SCOPUS:85029574383
SN - 2045-2322
VL - 7
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 11762
ER -
