Bioinformatic analysis of cis-regulatory interactions between progesterone and estrogen receptors in breast cancer — ASN Events

Bioinformatic analysis of cis-regulatory interactions between progesterone and estrogen receptors in breast cancer (#65)

Matloob Khushi 1 2 , Christine Clarke 2 , Dinny Graham 2
  1. Children Medical Research Institute, Westmead, NSW, Australia
  2. Westmead Institute for Cancer Research, Sydney Medical School, University of Sydney, Westmead, NSW, Australia

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 4358 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, one quarter of ERα binding sites overlapped with PR binding sites suggesting a biologically significant interaction on specific DNA regions. 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. Our data suggest that ERα and PR, in general function independently at the molecular level, but that their activities converge on a specific subset of transcriptional targets.