Bioinformatic analysis of cis-regulatory interactions between progesterone and estrogen receptors in breast cancer
Chromatin factors interact with each other in a cell and sequence-specific manner in order to regulate transcription and a wealth of publically available datasets exists describing the genomic locations of these interactions. Our recently published BiSA (Binding Sites Analyser) database contains tra...
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| Format: | Article |
| Language: | English |
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PeerJ Inc.
2014-11-01
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| Online Access: | https://peerj.com/articles/654.pdf |
| _version_ | 1827605731122085888 |
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| author | Matloob Khushi Christine L. Clarke J. Dinny Graham |
| author_facet | Matloob Khushi Christine L. Clarke J. Dinny Graham |
| author_sort | Matloob Khushi |
| collection | DOAJ |
| description | Chromatin factors interact with each other in a cell and sequence-specific manner in order to regulate transcription and a wealth of publically available datasets exists describing the genomic locations of these interactions. Our recently published BiSA (Binding Sites Analyser) database contains transcription factor binding locations and epigenetic modifications collected from published studies and provides tools to analyse stored and imported data. Using BiSA we investigated the overlapping cis-regulatory role of estrogen receptor alpha (ERα) and progesterone receptor (PR) in the T-47D breast cancer cell line. We found that ERα binding sites overlap with a subset of PR binding sites. To investigate further, we re-analysed raw data to remove any biases introduced by the use of distinct tools in the original publications. We identified 22,152 PR and 18,560 ERα binding sites (<5% false discovery rate) with 4,358 overlapping regions among the two datasets. BiSA statistical analysis revealed a non-significant overall overlap correlation between the two factors, suggesting that ERα and PR are not partner factors and do not require each other for binding to occur. However, Monte Carlo simulation by Binary Interval Search (BITS), Relevant Distance, Absolute Distance, Jaccard and Projection tests by Genometricorr revealed a statistically significant spatial correlation of binding regions on chromosome between the two factors. Motif analysis revealed that the shared binding regions were enriched with binding motifs for ERα, PR and a number of other transcription and pioneer factors. Some of these factors are known to co-locate with ERα and PR binding. Therefore spatially close proximity of ERα binding sites with PR binding sites suggests that ERα and PR, in general function independently at the molecular level, but that their activities converge on a specific subset of transcriptional targets. |
| first_indexed | 2024-03-09T06:25:41Z |
| format | Article |
| id | doaj.art-3630c0554274498897a2c4a76a2c340a |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T06:25:41Z |
| publishDate | 2014-11-01 |
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| spelling | doaj.art-3630c0554274498897a2c4a76a2c340a2023-12-03T11:19:52ZengPeerJ Inc.PeerJ2167-83592014-11-012e65410.7717/peerj.654654Bioinformatic analysis of cis-regulatory interactions between progesterone and estrogen receptors in breast cancerMatloob Khushi0Christine L. Clarke1J. Dinny Graham2Centre for Cancer Research, Westmead Millennium Institute, Sydney Medical School—Westmead, University of Sydney, AustraliaCentre for Cancer Research, Westmead Millennium Institute, Sydney Medical School—Westmead, University of Sydney, AustraliaCentre for Cancer Research, Westmead Millennium Institute, Sydney Medical School—Westmead, University of Sydney, AustraliaChromatin factors interact with each other in a cell and sequence-specific manner in order to regulate transcription and a wealth of publically available datasets exists describing the genomic locations of these interactions. Our recently published BiSA (Binding Sites Analyser) database contains transcription factor binding locations and epigenetic modifications collected from published studies and provides tools to analyse stored and imported data. Using BiSA we investigated the overlapping cis-regulatory role of estrogen receptor alpha (ERα) and progesterone receptor (PR) in the T-47D breast cancer cell line. We found that ERα binding sites overlap with a subset of PR binding sites. To investigate further, we re-analysed raw data to remove any biases introduced by the use of distinct tools in the original publications. We identified 22,152 PR and 18,560 ERα binding sites (<5% false discovery rate) with 4,358 overlapping regions among the two datasets. BiSA statistical analysis revealed a non-significant overall overlap correlation between the two factors, suggesting that ERα and PR are not partner factors and do not require each other for binding to occur. However, Monte Carlo simulation by Binary Interval Search (BITS), Relevant Distance, Absolute Distance, Jaccard and Projection tests by Genometricorr revealed a statistically significant spatial correlation of binding regions on chromosome between the two factors. Motif analysis revealed that the shared binding regions were enriched with binding motifs for ERα, PR and a number of other transcription and pioneer factors. Some of these factors are known to co-locate with ERα and PR binding. Therefore spatially close proximity of ERα binding sites with PR binding sites suggests that ERα and PR, in general function independently at the molecular level, but that their activities converge on a specific subset of transcriptional targets.https://peerj.com/articles/654.pdfTranscription factorsEstrogen receptor alphaProgesterone receptorERαESR1PR |
| spellingShingle | Matloob Khushi Christine L. Clarke J. Dinny Graham Bioinformatic analysis of cis-regulatory interactions between progesterone and estrogen receptors in breast cancer PeerJ Transcription factors Estrogen receptor alpha Progesterone receptor ERα ESR1 PR |
| title | Bioinformatic analysis of cis-regulatory interactions between progesterone and estrogen receptors in breast cancer |
| title_full | Bioinformatic analysis of cis-regulatory interactions between progesterone and estrogen receptors in breast cancer |
| title_fullStr | Bioinformatic analysis of cis-regulatory interactions between progesterone and estrogen receptors in breast cancer |
| title_full_unstemmed | Bioinformatic analysis of cis-regulatory interactions between progesterone and estrogen receptors in breast cancer |
| title_short | Bioinformatic analysis of cis-regulatory interactions between progesterone and estrogen receptors in breast cancer |
| title_sort | bioinformatic analysis of cis regulatory interactions between progesterone and estrogen receptors in breast cancer |
| topic | Transcription factors Estrogen receptor alpha Progesterone receptor ERα ESR1 PR |
| url | https://peerj.com/articles/654.pdf |
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