Global profiling of histone and DNA methylation reveals epigenetic-based regulation of gene expression during epithelial to mesenchymal transition in prostate cells.
Global profiling of histone and DNA methylation reveals epigenetic-based regulation of gene expression during epithelial to mesenchymal transition in prostate cells.
复制标题
DOI：
10.1186/1471-2164-11-669
复制
发表时间：
2010-11-25
期刊：
影响因子：
4.4
通讯作者：
Kalland KH
中科院分区：
文献类型：
--
作者：
Ke XS;Qu Y;Cheng Y;Li WC;Rotter V;Øyan AM;Kalland KH
先前我们报道了原发性前列腺细胞上皮细胞向间充质细胞转化（EMT）过程中广泛的基因表达重编程。在这里，我们研究了特定组蛋白和DNA甲基化参与EMT过程中基因表达协调的假设。组蛋白甲基化（H3K4me3和H3K27me3）和DNA甲基化（DNAMe）的全基因组谱分析应用于三个细胞系在不同阶段的逐步前列腺细胞模型，涉及EMT和随后的恶性特征积累。对表观遗传启动子修饰和基因表达变化的综合分析表明，组蛋白甲基化的动态变化与基因表达之间存在很强的相关性。DNA甲基化与整体基因抑制的相关性较弱，但当排除H3K4me3共修饰的基因时，与基因沉默的相关性很强。对于在启动子中标记有多个表观遗传标记的基因，转录水平与激活标记H3K4me3减去抑制标记H3K27me3或DNAMe的净信号强度相关，表明二价标记（H3K4/K27me3或H3K4me3/DNAMe）对基因表达的影响取决于相对修饰强度。上皮细胞连接和EMT相关的成纤维细胞生长因子受体基因在EMT过程中表现出相应的表观遗传修饰和基因表达变化。这项工作展示了上皮细胞系及其子代在EMT过程中表观遗传修饰的第一张蓝图，并表明特异性组蛋白甲基化广泛参与EMT过程中的基因表达重编程和随后的恶性特征积累。双价标记基因的转录活性取决于个体标记的相对标记强度，这一发现为表观遗传修饰的定量调控提供了新的视角。
Previously we reported extensive gene expression reprogramming during epithelial to mesenchymal transition (EMT) of primary prostate cells. Here we investigated the hypothesis that specific histone and DNA methylations are involved in coordination of gene expression during EMT. Genome-wide profiling of histone methylations (H3K4me3 and H3K27me3) and DNA methylation (DNAMe) was applied to three cell lines at different stages of a stepwise prostate cell model involving EMT and subsequent accumulation of malignant features. Integrated analyses of epigenetic promoter modifications and gene expression changes revealed strong correlations between the dynamic changes of histone methylations and gene expression. DNA methylation was weaker associated with global gene repression, but strongly correlated to gene silencing when genes co-modified by H3K4me3 were excluded. For genes labeled with multiple epigenetic marks in their promoters, the level of transcription was associated with the net signal intensity of the activating mark H3K4me3 minus the repressive marks H3K27me3 or DNAMe, indicating that the effect on gene expression of bivalent marks (H3K4/K27me3 or H3K4me3/DNAMe) depends on relative modification intensities. Sets of genes, including epithelial cell junction and EMT associated fibroblast growth factor receptor genes, showed corresponding changes concerning epigenetic modifications and gene expression during EMT. This work presents the first blueprint of epigenetic modifications in an epithelial cell line and the progeny that underwent EMT and shows that specific histone methylations are extensively involved in gene expression reprogramming during EMT and subsequent accumulation of malignant features. The observation that transcription activity of bivalently marked genes depends on the relative labeling intensity of individual marks provides a new view of quantitative regulation of epigenetic modification.
登录
查看更多内容
影响因子：
8
作者：
Jang, JH
通讯作者：
Jang, JH
DOI：
10.1073/pnas.0805206105
发表时间：
2008-09-16
影响因子：
11.1
作者：
Bloushtain-Qimron, Noga;Yao, Jun;Polyak, Kornelia
通讯作者：
Polyak, Kornelia
影响因子：
50.3
作者：
Acevedo, Victor D.;Gangula, Rama D.;Spencer, David M.
通讯作者：
Spencer, David M.
影响因子：
23.9
作者：
Fouse, Shaun D.;Shen, Yin;Fan, Guoping
通讯作者：
Fan, Guoping
影响因子：
23.9
作者：
Cui K;Zang C;Roh TY;Schones DE;Childs RW;Peng W;Zhao K
通讯作者：
Zhao K