Wang Xiao-Hui, Zhang Shu-Feng, Wu Hai-Ying, Gao Jian, Wang Lin, Yin Yao, Wang Xuhui
Department of Pediatric Surgery, Henan Provincial People's Hospital, Zhengzhou, China.
Department of Obstetrics, Henan Provincial People's Hospital, Zhengzhou, China.
Front Genet. 2025 Feb 17;16:1396073. doi: 10.3389/fgene.2025.1396073. eCollection 2025.
Gene expression is abnormal in disease compared to normal tissue same as the regulatory elements. Regulatory element binding with transcription factors managed transcription of gene, which usually require chromatin accessible.
To reveal potential epigenetic mechanism during hydronephrosis, we first used RNA-seq to finger out the disfunction genes during hydronephrosis, then combined with ATAC-seq, and BS-seq to reveal the related disfunction regulatory elements.
Finally, we find that 860 differentially genes and 2429 dynamic chromatin open regions between normal and hydronephrosis tissue. Though, most of disfunction genes and regulatory elements significantly enriched in chronic kidney disease GO term, only small part of regulatory element target genes overlapped with truly disfunction genes. And we also find out an important gene OTUD6B, which overexpression in disease tissue is manipulated by distal regulatory element through chromatin loop, and confirm the importance of epigenetic mechanism in disease.
In summary, we found many hub genes and potential therapeutic target during hydronephrosis, and also confirmed that epigenetic play important role in gene expression and relevant in disease progress.
与正常组织相比,疾病中的基因表达以及调控元件均存在异常。调控元件与转录因子结合以调控基因转录,这通常需要染色质处于可及状态。
为揭示肾积水过程中潜在的表观遗传机制,我们首先利用RNA测序找出肾积水过程中功能失调的基因,然后结合ATAC测序和BS测序以揭示相关的功能失调调控元件。
最终,我们发现正常组织与肾积水组织之间存在860个差异基因和2429个动态染色质开放区域。然而,大多数功能失调基因和调控元件在慢性肾病基因本体术语中显著富集,只有一小部分调控元件靶基因与真正的功能失调基因重叠。我们还发现了一个重要基因OTUD6B,其在疾病组织中的过表达受远端调控元件通过染色质环的调控,并证实了表观遗传机制在疾病中的重要性。
总之,我们在肾积水过程中发现了许多关键基因和潜在治疗靶点,同时也证实了表观遗传在基因表达及疾病进展中发挥着重要作用。