The androgen receptor cistrome is extensively reprogrammed in human prostate tumorigenesis
Open accessAbstract
Master transcription factors interact with DNA to establish cell type identity and to regulate gene expression in mammalian cells. The genome-wide map of these transcription factor binding sites has been termed the cistrome. Here we show that the androgen receptor (AR) cistrome undergoes extensive reprogramming during prostate epithelial transformation in man. Using human prostate tissue, we observed a core set of AR binding sites that are consistently reprogrammed in tumors. FOXA1 and HOXB13 colocalized at the reprogrammed AR binding sites in human tumor tissue. Introduction of FOXA1 and HOXB13 into an immortalized prostate cell line reprogrammed the AR cistrome to resemble that of a prostate tumor, functionally linking these specific factors to AR cistrome reprogramming. These findings offer mechanistic insights into a key set of events that drive normal prostate epithelium toward transformation and establish the centrality of epigenetic reprogramming in human prostate tumorigenesis.
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Key genes that drive PCa, such as FOXA1 or HOXB13, promote tumor progression by regulating how AR binds to or activates its target genes.
“many key genes that drive PCa, such as FOXA1 or HOXB13 (refs. 7,8), promote tumor progression by regulating how AR binds to or activates its target genes.”
From Genome-scale CRISPR screens identify PTGES3 as a direct modulator of androgen receptor function in advanced prostate cancer (2025) · cites this paper as [7]
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References 38 · Cited by 470
- Authors
- Pomerantz, M. M., Li, F., Takeda, D. Y., Lenci, R., Chonkar, A., Chabot, M., Cejas, P., Vazquez, F., Cook, J., Shivdasani, R. A., Bowden, M., Lis, R., Hahn, W. C., Kantoff, P. W., Brown, M., Loda, M., Long, H. W., & Freedman, M. L.
- Affiliations
- Harvard University (US)
- Dana-Farber Cancer Institute (US)
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Freedman, Matthew L
- ORCID
- Venue
- Nature Genetics
- Published
- 2015-10-12
- Volume
- 47
- Issue
- 11
- Pages
- 1346-1351
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC4707683
- OpenAlex
- W1951061860
- Cited by
- 470
- References
- 38
- Citations by year
- 2026: 36 · 2025: 49 · 2024: 44 · 2023: 52 · 2022: 49 · 2021: 58 · 2020: 37 · 2019: 46 · 2018: 38 · 2017: 37 · 2016: 21 · 2014: 1
- FWCI
- 25.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Cancer Institute (P50CA090381, U19CA148537, P50CA90381-11, U01CA176058, R01CA193910, P30CA008748)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- androgen receptor, cistrome, prostate tumorigenesis, FOXA1, HOXB13, transcription factor binding sites, epigenetic reprogramming, transcriptional reprogramming, prostate cancer
- MeSH terms
- Binding Sites, Cell Transformation, Neoplastic, Humans, Male, Prostate, Prostatic Neoplasms, Protein Binding, Receptors, Androgen, Immunoblotting, Cluster Analysis, Sequence Analysis, DNA, Homeodomain Proteins, RNA Interference, Cell Line, Tumor, Chromatin Immunoprecipitation, Hepatocyte Nuclear Factor 3-alpha, Kaplan-Meier Estimate, Genome-Wide Association Study, Transcriptome, Carcinogenesis
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