Histone H2A.Z prepares the prostate specific antigen (PSA) gene for androgen receptor-mediated transcription and is upregulated in a model of prostate cancer progression

The histone variant H2A.Z is present at many eukaryotic gene regulatory regions and can affect rates of transcription. Here we show that total H2A.Z and an acetylated form of H2A.Z is mainly present at the prostate specific antigen (PSA) enhancer and promoter in prostate cancer cell lines where the gene is expressed, but the levels decrease during rapid cycles of transcription. Treatment of prostate cancer cells with androgen results in increased H2A.Z levels due to upregulation of the H2A.Z-1, but not the H2A.Z-2 gene. This upregulation is likely the result of increased MYC transcription factor binding that occurs in response to androgen at the H2A.Z-1 promoter. Furthermore, we show that in a LNCaP xenograft model of prostate cancer progression, there is a significant increase of H2A.Z protein in castration resistant LNCaP tumors resulting from increased expression of the H2A.Z-1 gene. While a similar trend was observed in samples from prostate cancer patients, the results were not statistically significant. Nevertheless, there may be a subset of prostate cancers where elevated expression of H2A.Z-1 is indicative of prostate cancer progression to androgen independence.