The androgen receptor cistrome is extensively reprogrammed in human prostate tumorigenesis

By M. Pomerantz, Fugen Li, D. Takeda, Romina Lenci, Apurva Chonkar, Matthew S. Chabot, P. Cejas, F. Vazquez, J. Cook, R. Shivdasani and 8 more. 2015

424 citations recorded by the source corpus.

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.

Subfields: Molecular Biology, Pulmonary and Respiratory Medicine

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In Molecular Biology

1. Dirk Schübeler
2. Jussi Taipale
3. Paul Adrian Ginno
4. P. Beachy
5. Benjamin L. Ebert
6. Siddhartha Jaiswal

Citations in the corpus

• Impact of cytosine methylation on DNA binding specificities of human transcription factors (2017, background): “It has been previously shown that the chromatin state of normal prostate epithelium cells becomes more similar to that of prostate cancer cells upon expression of exogenous HOXB13 and FOXA1 (54).”