银屑病是一种以角化过度和角化过度为特征的慢性过度增生性皮肤病,门罗微脓肿,网钉的伸长,颗粒细胞变薄,和淋巴细胞浸润。我们先前通过转录组测序和ATAC-seq分析了银屑病皮肤的基因表达和染色质可及性。然而,缺乏整合这两个数据集来解开基因表达调控。这里,我们整合了相同银屑病和正常皮肤组织的转录组和ATAC-seq,试图利用染色质可及性的潜在作用及其在组织病理学特征中的功能。
通过诱导结合和表达靶标分析(BETA)算法,我们探索了15个银屑病皮肤和19个对照皮肤中转录因子结合的目标预测。BETA鉴定了408个上调的基因(等级乘积<0.01)和133个与染色质可及性相关的下调基因。我们注意到上调组基因的累积分数在统计学上高于背景,而下调组的基因表达不显著。KEGG通路分析显示,上调的408个基因富含TNF,点头,和IL-17信号通路。此外,BETA中的基序模块提示转录因子AP-1靶向了57个上调的基因,这表明染色质可及性的增加促进了AP-1与靶区域的结合,并进一步诱导了相关基因的表达.在这些基因中,SQLE,STRN,角化过度患者的EIF4和MYO1B表达增加,角化不全,和棘皮增厚。
总之,利用BETA的优势,我们确定了一系列有助于疾病发病机制的基因,特别是在调节组织病理学特征方面,为我们提供治疗牛皮癣的新线索。
Psoriasis is a chronic and hyperproliferative skin disease featured by hyperkeratosis with parakeratosis, Munro micro-abscess, elongation of rete pegs, granulosa thinning, and lymphocyte infiltration. We previously profiled gene expression and chromatin accessibility of psoriatic skins by transcriptome sequencing and ATAC-seq. However, integrating both of these datasets to unravel gene expression regulation is lacking. Here, we integrated transcriptome and ATAC-seq of the same psoriatic and normal skin tissues, trying to leverage the potential role of chromatin accessibility and their function in histopathology features.
By inducing binding and expression target analysis (
BETA) algorithms, we explored the target prediction of transcription factors binding in 15 psoriatic and 19 control skins.
BETA identified 408 upregulated genes (rank product < 0.01) and 133 downregulated genes linked with chromatin accessibility. We noticed that cumulative fraction of genes in upregulation group was statistically higher than background, while that of genes in downregulation group was not significant. KEGG pathway analysis showed that the upregulated 408 genes were enriched in TNF, NOD, and IL-17 signaling pathways. In addition, the motif module in
BETA suggested the 57 upregulated genes are targeted by transcription factor AP-1, indicating that increased chromatin accessibility facilitated the binding of AP-1 to the target regions and further induced expression of relevant genes. Among these genes, SQLE, STRN, EIF4, and MYO1B expression was increased in patients with hyperkeratosis, parakeratosis, and acanthosis thickening.
In summary, with the advantage of
BETA, we identified a series of genes that contribute to the disease pathogenesis, especially in modulating histopathology features, providing us with new clues in treating psoriasis.