Genomic androgen receptor-occupied regions with different functions, defined by histone acetylation, coregulators and transcriptional capacity.
Genomic androgen receptor-occupied regions with different functions, defined by histone acetylation, coregulators and transcriptional capacity.
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DOI：
10.1371/journal.pone.0003645
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发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Coetzee, Gerhard A.
中科院分区：
文献类型：
--
作者：
Jia, Li;Berman, Benjamin P.;Jariwala, Unnati;Yan, Xiting;Cogan, Jon P.;Walters, Allison;Chen, Ting;Buchanan, Grant;Frenkel, Baruch;Coetzee, Gerhard A.
雄激素受体（AR）是一种类固醇激活的转录因子，结合在特定的DNA位置，并在前列腺癌的病因学中发挥关键作用。虽然许多研究已经确定了AR结合和靶基因表达之间的明确联系，为有限数量的基因座，高通量阐明这些网站允许更深入地了解这个过程的复杂性。我们利用染色质免疫沉淀（ChIP）微阵列分析，将189个AR占据区域（ARORs）和1，388个组蛋白H3乙酰化（AcH 3）位点映射到3%连续延伸的人类基因组DNA。在62个高度可重复的AROR中，有32个（52%）也被AcH 3标记。虽然在前列腺癌细胞中检测到的AROR的数量超过了附近的DHT反应基因的数量，但AcH 3标记定义了一个与这些基因高度相关的AROR亚类-AcH 3 + AROR侧翼的基因中有12%是DHT反应基因，而AcH 3 − AROR侧翼的基因只有1%。大多数AROR含有增强子活性，如在荧光素酶报告基因测定中检测到的。通过分析AROR序列，然后进行定点ChIP，确定了AR转录辅助调节因子FoxA 1、CEBPβ、NFI和GATA 2的结合位点，这些位点在siRNA敲除实验中对内源性AR靶基因表达水平具有不同的影响。我们认为，只有一些ARORs的功能在给定的生理条件下，利用不同的机制。这种多样性表明了与染色质结构相关的相同转录因子对基因表达的差异调节。
The androgen receptor (AR) is a steroid-activated transcription factor that binds at specific DNA locations and plays a key role in the etiology of prostate cancer. While numerous studies have identified a clear connection between AR binding and expression of target genes for a limited number of loci, high-throughput elucidation of these sites allows for a deeper understanding of the complexities of this process. We have mapped 189 AR occupied regions (ARORs) and 1,388 histone H3 acetylation (AcH3) loci to a 3% continuous stretch of human genomic DNA using chromatin immunoprecipitation (ChIP) microarray analysis. Of 62 highly reproducible ARORs, 32 (52%) were also marked by AcH3. While the number of ARORs detected in prostate cancer cells exceeded the number of nearby DHT-responsive genes, the AcH3 mark defined a subclass of ARORs much more highly associated with such genes – 12% of the genes flanking AcH3+ARORs were DHT-responsive, compared to only 1% of genes flanking AcH3−ARORs. Most ARORs contained enhancer activities as detected in luciferase reporter assays. Analysis of the AROR sequences, followed by site-directed ChIP, identified binding sites for AR transcriptional coregulators FoxA1, CEBPβ, NFI and GATA2, which had diverse effects on endogenous AR target gene expression levels in siRNA knockout experiments. We suggest that only some ARORs function under the given physiological conditions, utilizing diverse mechanisms. This diversity points to differential regulation of gene expression by the same transcription factor related to the chromatin structure.
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影响因子：
9.8
作者：
Li XY;MacArthur S;Bourgon R;Nix D;Pollard DA;Iyer VN;Hechmer A;Simirenko L;Stapleton M;Luengo Hendriks CL;Chu HC;Ogawa N;Inwood W;Sementchenko V;Beaton A;Weiszmann R;Celniker SE;Knowles DW;Gingeras T;Speed TP;Eisen MB;Biggin MD
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Biggin MD
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30.8
作者：
Carroll, Jason S.;Meyer, Clifford A.;Brown, Myles
通讯作者：
Brown, Myles
影响因子：
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作者：
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通讯作者：
Liu XS
影响因子：
4.1
作者：
González, MI;Tovaglieri, A;Robins, DM
通讯作者：
Robins, DM
影响因子：
11.2
作者：
Jia, L;Choong, CSY;Coetzee, GA
通讯作者：
Coetzee, GA