Wenrong Xu1,2, Yan Li3,4, Yujie Dong1,3,4, Libo Xiao1,3,4, Lan Li5,6, Kangwei Jiao7,8,9. 1. Kunming Medical University, Kunming, 650500, Yunnan, China. 2. Department of Ophthalmology, The Affiliated Calmette Hospital of Kunming Medical University, 650024, Kunming, Yunnan, China. 3. Department of Ophthalmology, Affiliated Hospital of Yunnan University, Yunnan University, 650021, Kunming, China. 4. Key Laboratory of Yunnan Province, Yunnan Eye Institute, Yunnan University, 176 Qingnian, Kunming, 650021, China. 5. Kunming Medical University, Kunming, 650500, Yunnan, China. 641106144@qq.com. 6. Department of Ophthalmology, The Affiliated Calmette Hospital of Kunming Medical University, 650024, Kunming, Yunnan, China. 641106144@qq.com. 7. Kunming Medical University, Kunming, 650500, Yunnan, China. Kangwei.jiao@ynu.edu.cn. 8. Department of Ophthalmology, Affiliated Hospital of Yunnan University, Yunnan University, 650021, Kunming, China. Kangwei.jiao@ynu.edu.cn. 9. Key Laboratory of Yunnan Province, Yunnan Eye Institute, Yunnan University, 176 Qingnian, Kunming, 650021, China. Kangwei.jiao@ynu.edu.cn.
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.
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.