Table 2_Alteration of chromatin states perturb the transcription regulation of gene during hydronephrosis.xls

BackgroundGene 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.
MethodsTo 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.
ResultsFinally, 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.
ConclusionIn 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.

背景：与正常组织相比，疾病状态下的基因表达与调控元件（regulatory element）均存在异常。转录因子（transcription factor）结合的调控元件负责调控基因的转录，这一过程通常依赖染色质（chromatin）的开放状态。
方法：为揭示肾积水（hydronephrosis）发生过程中的潜在表观遗传调控机制，本研究首先通过RNA测序（RNA-seq）筛选肾积水状态下的功能异常基因，随后结合转座酶可及性测序（ATAC-seq）与亚硫酸氢盐测序（BS-seq），以鉴定相关的功能异常调控元件。
结果：最终，我们在正常组织与肾积水组织间鉴定出860个差异表达基因与2429个动态染色质开放区域。尽管多数功能异常基因与调控元件显著富集于慢性肾脏病的基因本体（GO, Gene Ontology）功能注释条目，但仅有小部分调控元件的靶基因与实际的功能异常基因存在重叠。此外，本研究还发现了关键基因OTUD6B：该基因在疾病组织中的过表达由远端调控元件通过染色质环（chromatin loop）调控，并证实了表观遗传机制在疾病发生中的重要作用。
结论：综上，本研究鉴定出肾积水发生过程中的多个核心基因（hub gene）与潜在治疗靶点，同时证实表观遗传机制在基因表达调控中发挥重要作用，并与疾病进展密切相关。