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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Sci+Rep
2017 ; 7
(1
): 11762
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DNA Methylomes Reveal Biological Networks Involved in Human Eye Development,
Functions and Associated Disorders
#MMPMID28924151
Berdasco M
; Gómez A
; Rubio MJ
; Català-Mora J
; Zanón-Moreno V
; Lopez M
; Hernández C
; Yoshida S
; Nakama T
; Ishikawa K
; Ishibashi T
; Boubekeur AM
; Louhibi L
; Pujana MA
; Sayols S
; Setien F
; Corella D
; de Torres C
; Parareda A
; Mora J
; Zhao L
; Zhang K
; Lleonart ME
; Alonso J
; Simó R
; Caminal JM
; Esteller M
Sci Rep
2017[Sep]; 7
(1
): 11762
PMID28924151
show ga
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.