Non-overlapping progesterone receptor cistromes contribute to cell-specific transcriptional outcomes.
Non-overlapping progesterone receptor cistromes contribute to cell-specific transcriptional outcomes.
复制标题
DOI：
10.1371/journal.pone.0035859
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Graham JD
中科院分区：
文献类型：
--
作者：
Clarke CL;Graham JD
卵巢激素黄体酮的转录作用是多效的，结合核黄体酮受体（PR）的DNA，一种配体激活的转录因子，在一系列靶组织中导致不同的结果。为了确定PR基因组相互作用的不同模式是否有助于PR转录组的细胞特异性，我们比较了PR在乳腺癌细胞和永生化正常乳腺细胞中的基因组结合位点。在两种细胞系中，PR结合与转录结果相关，60%的孕激素调节基因与一个或多个PR结合区相关。两种细胞系的PR细胞基质之间的重叠非常低，转录靶点的重叠也同样低。在两种细胞系的PR结合区都发现了一个保守的PR结合元件，但已知的辅助因子结合基序的富集模式不同，FOXA1位点在乳腺癌细胞结合区过度代表，NF1和AP-1基序在永活正常细胞系中独特富集。下游分析表明，不同的辅助因子可用性可能产生这些不同的PR池，表明辅助因子水平可能调节PR特异性。综上所述，这些数据表明PR结合的细胞特异性是由关键结合辅因子的协同作用决定的。
The transcriptional effects of the ovarian hormone progesterone are pleiotropic, and binding to DNA of the nuclear progesterone receptor (PR), a ligand-activated transcription factor, results in diverse outcomes in a range of target tissues. To determine whether distinct patterns of genomic interaction of PR contribute to the cell specificity of the PR transcriptome, we have compared the genomic binding sites for PR in breast cancer cells and immortalized normal breast cells. PR binding was correlated with transcriptional outcome in both cell lines, with 60% of progestin-regulated genes associated with one or more PR binding regions. There was a remarkably low overlap between the PR cistromes of the two cell lines, and a similarly low overlap in transcriptional targets. A conserved PR binding element was identified in PR binding regions from both cell lines, but there were distinct patterns of enrichment of known cofactor binding motifs, with FOXA1 sites over-represented in breast cancer cell binding regions and NF1 and AP-1 motifs uniquely enriched in the immortalized normal line. Downstream analyses suggested that differential cofactor availability may generate these distinct PR cistromes, indicating that cofactor levels may modulate PR specificity. Taken together these data suggest that cell-specificity of PR binding is determined by the coordinated effects of key binding cofactors.
登录
查看更多内容
影响因子：
3
作者：
Bailey TL;Bodén M;Whitington T;Machanick P
通讯作者：
Machanick P
影响因子：
64.5
作者：
Garcia-Bassets, Ivan;Kwon, Young-Soo;Rosenfeld, Michael G.
通讯作者：
Rosenfeld, Michael G.
影响因子：
30.8
作者：
Carroll, Jason S.;Meyer, Clifford A.;Brown, Myles
通讯作者：
Brown, Myles
影响因子：
4.8
作者：
Graham, J. Dinny;Mote, Patricia A.;Clarke, Christine L.
通讯作者：
Clarke, Christine L.
DOI：
10.1093/jnci/djq527
发表时间：
2011-02-16
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Beral V;Reeves G;Bull D;Green J;Million Women Study Collaborators
通讯作者：
Million Women Study Collaborators