肾积水时染色质状态的改变扰乱了基因的转录调控。

IF 3 3区 生物学 Q2 GENETICS & HEREDITY Frontiers in Genetics Pub Date : 2025-02-17 eCollection Date: 2025-01-01 DOI:10.3389/fgene.2025.1396073
Xiao-Hui Wang, Shu-Feng Zhang, Hai-Ying Wu, Jian Gao, Lin Wang, Yao Yin, Xuhui Wang
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引用次数: 0

摘要

背景:与正常组织相比,疾病中的基因表达与调节元件一样是异常的。调控元件结合转录因子管理基因的转录,这通常需要染色质可及。方法:为了揭示肾积水过程中潜在的表观遗传机制,我们首先利用RNA-seq找出肾积水过程中的功能障碍基因,然后结合ATAC-seq、BS-seq揭示相关功能障碍调控元件。结果:在肾积水组织和正常组织中发现了860个差异基因和2429个动态染色质开放区。虽然大多数功能障碍基因和调控元件在慢性肾病GO期显著富集,但只有一小部分调控元件靶基因与真正的功能障碍基因重叠。我们还发现了一个重要的基因OTUD6B,该基因在疾病组织中的过表达受远端调控元件通过染色质环操纵,证实了表观遗传机制在疾病中的重要性。结论:综上所述,我们在肾积水中发现了许多中枢基因和潜在的治疗靶点,也证实了表观遗传在基因表达和疾病进展中起重要作用。
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Alteration of chromatin states perturb the transcription regulation of gene during hydronephrosis.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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来源期刊
Frontiers in Genetics
Frontiers in Genetics Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
5.50
自引率
8.10%
发文量
3491
审稿时长
14 weeks
期刊介绍: Frontiers in Genetics publishes rigorously peer-reviewed research on genes and genomes relating to all the domains of life, from humans to plants to livestock and other model organisms. Led by an outstanding Editorial Board of the world’s leading experts, this multidisciplinary, open-access journal is at the forefront of communicating cutting-edge research to researchers, academics, clinicians, policy makers and the public. The study of inheritance and the impact of the genome on various biological processes is well documented. However, the majority of discoveries are still to come. A new era is seeing major developments in the function and variability of the genome, the use of genetic and genomic tools and the analysis of the genetic basis of various biological phenomena.
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