Global Analysis of Transcription Start Sites and Enhancers in Endometrial Stromal Cells and Differences Associated with Endometriosis
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) samp...
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| Format: | Article |
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MDPI AG
2023-06-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/13/1736 |
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| author | Sushma Marla Sally Mortlock Sohye Yoon Joanna Crawford Stacey Andersen Michael D. Mueller Brett McKinnon Quan Nguyen Grant W. Montgomery |
| author_facet | Sushma Marla Sally Mortlock Sohye Yoon Joanna Crawford Stacey Andersen Michael D. Mueller Brett McKinnon Quan Nguyen Grant W. Montgomery |
| author_sort | Sushma Marla |
| collection | DOAJ |
| description | 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 (<i>n</i> = 4) and without endometriosis (<i>n</i> = 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 <i>IGFBP5, CALD1</i> and <i>OXTR</i>. 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. |
| first_indexed | 2024-03-11T01:44:58Z |
| format | Article |
| id | doaj.art-3487a2c21f20448eb09f5232b7137e46 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T01:44:58Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-3487a2c21f20448eb09f5232b7137e462023-11-18T16:19:19ZengMDPI AGCells2073-44092023-06-011213173610.3390/cells12131736Global Analysis of Transcription Start Sites and Enhancers in Endometrial Stromal Cells and Differences Associated with EndometriosisSushma Marla0Sally Mortlock1Sohye Yoon2Joanna Crawford3Stacey Andersen4Michael D. Mueller5Brett McKinnon6Quan Nguyen7Grant W. Montgomery8The Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, AustraliaThe Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, AustraliaThe Genome Innovation Hub, The University of Queensland, Brisbane, QLD 4072, AustraliaThe Genome Innovation Hub, The University of Queensland, Brisbane, QLD 4072, AustraliaThe Genome Innovation Hub, The University of Queensland, Brisbane, QLD 4072, AustraliaDepartment of Gynecology and Gynecological Oncology, Inselspital, Bern University Hospital, University of Bern, 3010 Berne, SwitzerlandThe Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, AustraliaThe Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, AustraliaThe Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, AustraliaIdentifying 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 (<i>n</i> = 4) and without endometriosis (<i>n</i> = 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 <i>IGFBP5, CALD1</i> and <i>OXTR</i>. 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.https://www.mdpi.com/2073-4409/12/13/1736endometrial stromal cellsCap analysis of gene expressiontranscription start sites |
| spellingShingle | Sushma Marla Sally Mortlock Sohye Yoon Joanna Crawford Stacey Andersen Michael D. Mueller Brett McKinnon Quan Nguyen Grant W. Montgomery Global Analysis of Transcription Start Sites and Enhancers in Endometrial Stromal Cells and Differences Associated with Endometriosis Cells endometrial stromal cells Cap analysis of gene expression transcription start sites |
| title | Global Analysis of Transcription Start Sites and Enhancers in Endometrial Stromal Cells and Differences Associated with Endometriosis |
| title_full | Global Analysis of Transcription Start Sites and Enhancers in Endometrial Stromal Cells and Differences Associated with Endometriosis |
| title_fullStr | Global Analysis of Transcription Start Sites and Enhancers in Endometrial Stromal Cells and Differences Associated with Endometriosis |
| title_full_unstemmed | Global Analysis of Transcription Start Sites and Enhancers in Endometrial Stromal Cells and Differences Associated with Endometriosis |
| title_short | Global Analysis of Transcription Start Sites and Enhancers in Endometrial Stromal Cells and Differences Associated with Endometriosis |
| title_sort | global analysis of transcription start sites and enhancers in endometrial stromal cells and differences associated with endometriosis |
| topic | endometrial stromal cells Cap analysis of gene expression transcription start sites |
| url | https://www.mdpi.com/2073-4409/12/13/1736 |
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