Massie Charles E, Mills Ian G
Cancer Research UK, Cambridge Research Institute, Cambridge, UK.
Methods Mol Biol. 2011;776:255-73. doi: 10.1007/978-1-61779-243-4_15.
Chromatin immunoprecipitation (ChIP) is an invaluable tool in the study of transcriptional regulation. ChIP methods require both a priori knowledge of the transcriptional regulators which are important for a given biological system and high-quality specific antibodies for these targets. The androgen receptor (AR) is known to play essential roles in male sexual development, in prostate cancer and in the function of many other AR-expressing cell types (e.g. neurons and myocytes). As a ligand-activated transcription factor the AR also represents an endogenous, inducible system to study transcriptional biology. Therefore, ChIP studies of the AR can make use of treatment contrast experiments to define its transcriptional targets. To date several studies have mapped AR binding sites using ChIP in combination with genome tiling microarrays (ChIP-chip) or direct sequencing (ChIP-seq), mainly in prostate cancer cell lines and with varying degrees of genomic coverage. These studies have provided new insights into the DNA sequences to which the AR can bind, identified AR cooperating transcription factors, mapped thousands of potential AR regulated genes and provided insights into the biological processes regulated by the AR. However, further ChIP studies will be required to fully characterise the dynamics of the AR-regulated transcriptional programme, to map the occupancy of different AR transcriptional complexes which result in different transcriptional output and to delineate the transcriptional networks downstream of the AR.
染色质免疫沉淀（ChIP）是转录调控研究中一项非常重要的工具。ChIP方法既需要对特定生物系统中重要的转录调节因子有先验知识，也需要针对这些靶点的高质量特异性抗体。已知雄激素受体（AR）在男性性发育、前列腺癌以及许多其他表达AR的细胞类型（如神经元和心肌细胞）的功能中发挥着重要作用。作为一种配体激活的转录因子，AR也是研究转录生物学的内源性可诱导系统。因此，对AR的ChIP研究可以利用处理对照实验来确定其转录靶点。迄今为止，已有多项研究结合基因组平铺微阵列（ChIP-chip）或直接测序（ChIP-seq），主要在前列腺癌细胞系中使用ChIP来绘制AR结合位点，且基因组覆盖程度各不相同。这些研究为AR能够结合的DNA序列提供了新的见解，鉴定了与AR协同作用的转录因子，绘制了数千个潜在的AR调控基因，并为AR调控的生物学过程提供了见解。然而，还需要进一步的ChIP研究来全面表征AR调控的转录程序的动态变化，绘制导致不同转录输出的不同AR转录复合物的占据情况，并描绘AR下游的转录网络。
