Genome-wide analysis of androgen receptor binding and transcriptomic analysis in mesenchymal subsets during prostate development
Prostate development is controlled by androgens, the androgen receptor (AR) and mesenchymal–epithelial signalling. We used chromatin immunoprecipitation sequencing (ChIP-seq) to define AR genomic binding in the male and female mesenchyme. Tissue- and single-cell-based transcriptional profiling was u...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2019-07-01
|
| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/12/7/dmm039297 |
| _version_ | 1818528044850085888 |
|---|---|
| author | Claire Nash Nadia Boufaied Dunarel Badescu Yu Chang Wang Miltiadis Paliouras Mark Trifiro Ioannis Ragoussis Axel A. Thomson |
| author_facet | Claire Nash Nadia Boufaied Dunarel Badescu Yu Chang Wang Miltiadis Paliouras Mark Trifiro Ioannis Ragoussis Axel A. Thomson |
| author_sort | Claire Nash |
| collection | DOAJ |
| description | Prostate development is controlled by androgens, the androgen receptor (AR) and mesenchymal–epithelial signalling. We used chromatin immunoprecipitation sequencing (ChIP-seq) to define AR genomic binding in the male and female mesenchyme. Tissue- and single-cell-based transcriptional profiling was used to define mesenchymal AR target genes. We observed significant AR genomic binding in females and a strong enrichment at proximal promoters in both sexes. In males, there was greater AR binding to introns and intergenic regions as well as to classical AR binding motifs. In females, there was increased proximal promoter binding and involvement of cofactors. Comparison of AR-bound genes with transcriptomic data enabled the identification of novel sexually dimorphic AR target genes. We validated the dimorphic expression of AR target genes using published datasets and confirmed regulation by androgens using ex vivo organ cultures. AR targets showed variable expression in patients with androgen insensitivity syndrome. We examined AR function at single-cell resolution using single-cell RNA sequencing (scRNA-seq) in male and female mesenchyme. Surprisingly, both AR and target genes were distributed throughout cell subsets, with few positive cells within each subset. AR binding was weakly correlated with target gene expression. |
| first_indexed | 2024-12-11T06:44:29Z |
| format | Article |
| id | doaj.art-7e03e3d0d6a242f59b5bd2f9c84c6536 |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-11T06:44:29Z |
| publishDate | 2019-07-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-7e03e3d0d6a242f59b5bd2f9c84c65362022-12-22T01:17:07ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112019-07-0112710.1242/dmm.039297039297Genome-wide analysis of androgen receptor binding and transcriptomic analysis in mesenchymal subsets during prostate developmentClaire Nash0Nadia Boufaied1Dunarel Badescu2Yu Chang Wang3Miltiadis Paliouras4Mark Trifiro5Ioannis Ragoussis6Axel A. Thomson7 Department of Surgery, Division of Urology, McGill University and the Cancer Research Program of the Research Institute of McGill University Health Centre, Montreal, Quebec, Canada H4A 3J1 Department of Surgery, Division of Urology, McGill University and the Cancer Research Program of the Research Institute of McGill University Health Centre, Montreal, Quebec, Canada H4A 3J1 McGill University and Genome Quebec Innovation Center, Montreal, Quebec, Canada H3A 0G1 McGill University and Genome Quebec Innovation Center, Montreal, Quebec, Canada H3A 0G1 Division of Endocrinology, Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital, 5750 Côte-des-Neiges Rd, Montreal, QC, Canada H3S 1Y9 Division of Endocrinology, Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital, 5750 Côte-des-Neiges Rd, Montreal, QC, Canada H3S 1Y9 McGill University and Genome Quebec Innovation Center, Montreal, Quebec, Canada H3A 0G1 Department of Surgery, Division of Urology, McGill University and the Cancer Research Program of the Research Institute of McGill University Health Centre, Montreal, Quebec, Canada H4A 3J1 Prostate development is controlled by androgens, the androgen receptor (AR) and mesenchymal–epithelial signalling. We used chromatin immunoprecipitation sequencing (ChIP-seq) to define AR genomic binding in the male and female mesenchyme. Tissue- and single-cell-based transcriptional profiling was used to define mesenchymal AR target genes. We observed significant AR genomic binding in females and a strong enrichment at proximal promoters in both sexes. In males, there was greater AR binding to introns and intergenic regions as well as to classical AR binding motifs. In females, there was increased proximal promoter binding and involvement of cofactors. Comparison of AR-bound genes with transcriptomic data enabled the identification of novel sexually dimorphic AR target genes. We validated the dimorphic expression of AR target genes using published datasets and confirmed regulation by androgens using ex vivo organ cultures. AR targets showed variable expression in patients with androgen insensitivity syndrome. We examined AR function at single-cell resolution using single-cell RNA sequencing (scRNA-seq) in male and female mesenchyme. Surprisingly, both AR and target genes were distributed throughout cell subsets, with few positive cells within each subset. AR binding was weakly correlated with target gene expression.http://dmm.biologists.org/content/12/7/dmm039297ChIP-seqAndrogen receptorRNA-seqSingle-cell RNA-seqMesenchymeProstate development |
| spellingShingle | Claire Nash Nadia Boufaied Dunarel Badescu Yu Chang Wang Miltiadis Paliouras Mark Trifiro Ioannis Ragoussis Axel A. Thomson Genome-wide analysis of androgen receptor binding and transcriptomic analysis in mesenchymal subsets during prostate development Disease Models & Mechanisms ChIP-seq Androgen receptor RNA-seq Single-cell RNA-seq Mesenchyme Prostate development |
| title | Genome-wide analysis of androgen receptor binding and transcriptomic analysis in mesenchymal subsets during prostate development |
| title_full | Genome-wide analysis of androgen receptor binding and transcriptomic analysis in mesenchymal subsets during prostate development |
| title_fullStr | Genome-wide analysis of androgen receptor binding and transcriptomic analysis in mesenchymal subsets during prostate development |
| title_full_unstemmed | Genome-wide analysis of androgen receptor binding and transcriptomic analysis in mesenchymal subsets during prostate development |
| title_short | Genome-wide analysis of androgen receptor binding and transcriptomic analysis in mesenchymal subsets during prostate development |
| title_sort | genome wide analysis of androgen receptor binding and transcriptomic analysis in mesenchymal subsets during prostate development |
| topic | ChIP-seq Androgen receptor RNA-seq Single-cell RNA-seq Mesenchyme Prostate development |
| url | http://dmm.biologists.org/content/12/7/dmm039297 |
| work_keys_str_mv | AT clairenash genomewideanalysisofandrogenreceptorbindingandtranscriptomicanalysisinmesenchymalsubsetsduringprostatedevelopment AT nadiaboufaied genomewideanalysisofandrogenreceptorbindingandtranscriptomicanalysisinmesenchymalsubsetsduringprostatedevelopment AT dunarelbadescu genomewideanalysisofandrogenreceptorbindingandtranscriptomicanalysisinmesenchymalsubsetsduringprostatedevelopment AT yuchangwang genomewideanalysisofandrogenreceptorbindingandtranscriptomicanalysisinmesenchymalsubsetsduringprostatedevelopment AT miltiadispaliouras genomewideanalysisofandrogenreceptorbindingandtranscriptomicanalysisinmesenchymalsubsetsduringprostatedevelopment AT marktrifiro genomewideanalysisofandrogenreceptorbindingandtranscriptomicanalysisinmesenchymalsubsetsduringprostatedevelopment AT ioannisragoussis genomewideanalysisofandrogenreceptorbindingandtranscriptomicanalysisinmesenchymalsubsetsduringprostatedevelopment AT axelathomson genomewideanalysisofandrogenreceptorbindingandtranscriptomicanalysisinmesenchymalsubsetsduringprostatedevelopment |