Volume 21 Issue 9
Sep.  2023
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WEI Ting, QI Xianjie, ZHANG Xu, WANG Yatao, JIANG Yiyao, SHI Chao. Investigation of the downstream target gene network regulated by KDM5A using ChIP-seq in Cardiac fibroblasts[J]. Chinese Journal of General Practice, 2023, 21(9): 1474-1477. doi: 10.16766/j.cnki.issn.1674-4152.003149
Citation: WEI Ting, QI Xianjie, ZHANG Xu, WANG Yatao, JIANG Yiyao, SHI Chao. Investigation of the downstream target gene network regulated by KDM5A using ChIP-seq in Cardiac fibroblasts[J]. Chinese Journal of General Practice, 2023, 21(9): 1474-1477. doi: 10.16766/j.cnki.issn.1674-4152.003149

Investigation of the downstream target gene network regulated by KDM5A using ChIP-seq in Cardiac fibroblasts

doi: 10.16766/j.cnki.issn.1674-4152.003149
Funds:

 81800214

 Byycx21077

  • Received Date: 2022-08-11
    Available Online: 2023-10-19
  •   Objective  To investigate the potential mechanism of KDM5A in regulating the biological function of cardiac fibroblasts.  Methods  Cardiac fibroblasts from patients with myocardial fibrosis were isolated and cultured, chromatin immunoprecipitation sequence (ChIP-seq) was performed to analyze immunoaffinity separation of specific binding DNA fragments with KDM5A for sequence identification, differentially expressed genes (DEGs) were screened for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis.  Results  The binding peak of KDM5A in the gene promoter region, intron region, and exon region accounted for 14.59%, 44.14% and 1.84%, respectively. Among them, the proportion of ≤1 kb, >1-2 kb and >2-3 kb promoter regions were 5.91%, 4.56% and 4.12%, respectively. The binding ratio of KDM5A to the first intron region and other intron regions were 12.19% and 31.95%, respectively. The distribution of KDM5A binding peaks relative to the transcription start site (TSS) was mainly concentrated at -3 to 3 kb, and the reads count frequency was the highest at the TSS coordinates -1.0 kb and 2.5 kb. Homer software was applied to identify 20 motifs that bind to KDM5A, including FOXE1, PB, ZNF460, etc. GO functional annotation analysis suggested that the KDM5A binding genes were involved in the regulation of cell morphogenesis, axon development, regulation of neuron projection development, plasma membrane protein complex, cation channel, actin cytoskeleton, metal ion transmembrane transporter activity, cation transmembrane transporter activity and GTP enzyme binding, etc. The KEGG signaling pathway enrichment results showed that KDM5A-related genes were significantly enriched in the phospholipase D signaling pathway, cholinergic synapse, calcium signaling pathways, Wnt signaling pathway, growth hormone synthesis, secretion and action, insulin secretion, ErbB signaling pathway and Rap1 signaling pathways, etc.  Conclusion  KDM5A regulates the transcription expression of genes and the expression of signal pathways, thereby affecting the function of cardiac fibroblasts and participating in the onset and development of myocardial fibrosis.

     

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