The Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
The Genome Innovation Hub, The University of Queensland, Brisbane, QLD 4072, Australia.
Cells. 2023 Jun 28;12(13):1736. doi: 10.3390/cells12131736.
Identifying tissue-specific molecular signatures of active regulatory elements is critical to understanding gene regulatory mechanisms. In this study, transcription start sites (TSS) and enhancers were identified using Cap analysis of gene expression (CAGE) across endometrial stromal cell (ESC) samples obtained from women with ( = 4) and without endometriosis ( = 4). ESC TSSs and enhancers were compared to those reported in other tissue and cell types in FANTOM5 and were integrated with RNA-seq and ATAC-seq data from the same samples for regulatory activity and network analyses. CAGE tag count differences between women with and without endometriosis were statistically tested and tags within close proximity to genetic variants associated with endometriosis risk were identified. Over 90% of tag clusters mapping to promoters were observed in cells and tissues in FANTOM5. However, some potential cell-type-specific promoters and enhancers were also observed. Regions of open chromatin identified using ATAC-seq provided further evidence of the active transcriptional regions identified by CAGE. Despite the small sample number, there was evidence of differences associated with endometriosis at 210 consensus clusters, including and . ESC TSSs were also located within loci associated with endometriosis risk from genome-wide association studies. This study provides novel evidence of transcriptional differences in endometrial stromal cells associated with endometriosis and provides a valuable cell-type specific resource of active TSSs and enhancers in endometrial stromal cells.
鉴定活跃调控元件的组织特异性分子特征对于理解基因调控机制至关重要。在这项研究中，使用基因表达的 CAGE 分析（Cap analysis of gene expression，CAGE）在来自患有子宫内膜异位症（= 4）和不患有子宫内膜异位症（= 4）的女性的子宫内膜基质细胞（endometrial stromal cell，ESC）样本中鉴定了转录起始位点（transcription start sites，TSS）和增强子。将 ESC TSS 和增强子与 FANTOM5 中报道的其他组织和细胞类型进行了比较，并与来自相同样本的 RNA-seq 和 ATAC-seq 数据进行了整合，用于调控活性和网络分析。对患有和不患有子宫内膜异位症的女性之间的 CAGE 标签计数差异进行了统计学检验，并鉴定了与子宫内膜异位症风险相关的遗传变异附近的标签。在 FANTOM5 中，超过 90%的映射到启动子的标签簇在细胞和组织中被观察到。然而，也观察到了一些潜在的细胞类型特异性启动子和增强子。使用 ATAC-seq 鉴定的开放染色质区域为 CAGE 鉴定的活跃转录区域提供了进一步的证据。尽管样本数量较少，但在 210 个共识簇中发现了与子宫内膜异位症相关的差异证据，包括 和 。ESC TSS 也位于全基因组关联研究中与子宫内膜异位症风险相关的基因座内。这项研究提供了子宫内膜基质细胞中与子宫内膜异位症相关的转录差异的新证据，并提供了子宫内膜基质细胞中活跃 TSS 和增强子的宝贵细胞类型特异性资源。
