Integrative RNA-seq and ATAC-seq analyses of phosphodiesterase 6 mutation-induced retinitis pigmentosa.
Int Ophthalmol
; 42(8): 2385-2395, 2022 Aug.
Article
em En
| MEDLINE
| ID: mdl-35147831
ABSTRACT
PURPOSE:
Inhibition of poly-ADP-ribose polymerase 1 (PARP1) could relieve phosphodiesterase 6 mutation-induced retinitis pigmentosa (RP). However, the mechanism related to PARP1 overexpression in the RP has not been clarified. We attempted to explore the potential mechanism related to PARP1 regulating RP.METHODS:
ATAC-seq and RNA-seq were performed for retina tissues of C3H and rd1 mice. The differentially expressed genes (DEGs) were identified, followed by the construction of PARP1-DEG co-expression and protein-protein interaction (PPI) networks. Gene ontology-biological process and pathway enrichment of DEGs were performed by clusterProfiler software. The overlapped genes that might play regulatory roles in PARP1 expression were mined by integrated analysis of RNA-seq and ATAC-seq data.RESULTS:
A total of 1061 DEGs were identified between C3H and rd1 group. Co-expression network was constructed with 313 PARP1-gene co-expression pairs. The down-regulated DEGs were closely related to visual perception and light stimulus-related biological process, while the up-regulated DEGs were significantly enriched in phototransduction and PPAR signaling pathway. PPI network was constructed with 202 nodes and 375 edges, which was clustered into 3 modules. Module 1 genes were closely related to detection of light stimulus, visual perception related biological process and phototransduction pathway (involved with Gnat1/Guca1b/Gnat2/Sag/Pde6g). By integrated analysis of the RNA-seq and ATAC-seq, the overlapped up-regulated genes were Asxl3 and Nyap2, while the down-regulated genes were Tmem136 and Susd3.CONCLUSION:
Gnat1 may play a key role in RP development by interacting with PARP1. Susd3 may play a regulatory role in PARP1 expression and affect RP formation.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Retinose Pigmentar
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Nucleotídeo Cíclico Fosfodiesterase do Tipo 6
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article