Department of Molecular and Cellular Biochemistry and the Comprehensive Cancer Center, The Ohio State University College of Medicine, Columbus, OH 43210, USA.
Trends Endocrinol Metab. 2011 Dec;22(12):474-80. doi: 10.1016/j.tem.2011.07.006. Epub 2011 Aug 31.
The androgen receptor (AR) is important for prostate cancer development and progression. Genome-wide mapping of AR binding sites in prostate cancer has found that the majority of AR binding sites are located within non-promoter regions. These distal AR binding regions regulate AR target genes (e.g. UBE2C) involved in prostate cancer growth through chromatin looping. In addition to long-distance gene regulation, looping has been shown to induce spatial proximity of two genes otherwise located far away along the genomic sequence and the formation of double-strand DNA breaks, resulting in aberrant gene fusions (e.g. TMPRSS2-ERG) that also contribute to prostate tumorigenesis. Elucidating the mechanisms of AR-driven chromatin looping will increase our understanding of prostate carcinogenesis and may lead to the identification of new therapeutic targets.
雄激素受体 (AR) 对前列腺癌的发生和发展至关重要。对前列腺癌中 AR 结合位点的全基因组作图发现，大多数 AR 结合位点位于非启动子区域内。这些远端 AR 结合区域通过染色质环化调节 AR 靶基因（例如 UBE2C），这些基因参与前列腺癌的生长。除了远距离基因调控外，环化还显示出诱导两个基因的空间接近性，否则这些基因沿着基因组序列的位置相距很远，形成双链 DNA 断裂，导致异常基因融合（例如 TMPRSS2-ERG），这也有助于前列腺肿瘤发生。阐明 AR 驱动的染色质环化机制将增加我们对前列腺癌发生的理解，并可能导致新的治疗靶点的鉴定。
