Chromatin poises miRNA- and protein-coding genes for expression
Chromatin poises miRNA- and protein-coding genes for expression
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DOI：
10.1101/gr.090951.109
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发表时间：
2009-10-01
期刊：
影响因子：
7
通讯作者：
Zhao, Keji
中科院分区：
文献类型：
--
作者：
Barski, Artem;Jothi, Raja;Zhao, Keji
染色质修饰与基因表达调控有关。虽然已经确定了某些修饰与表达或沉默基因的关联，但仍不清楚染色质环境的变化如何与基因表达的变化相关。在这篇文章中，我们使用ChIP-seq（染色质免疫沉淀与大规模平行测序）来分析通过T细胞受体（TCR）信号激活总人类CD 4（+）T细胞期间染色质修饰的全基因组变化。令人惊讶的是，我们发现在静息T细胞的短期激活期间，许多诱导和沉默基因的染色质修饰模式相对稳定。活性染色质修饰已经在大多数诱导蛋白编码基因的位置，即使这些基因在静息细胞中沉默。类似地，在T细胞活化时沉默的基因即使在沉默后也保留阳性染色质修饰。为了研究这些观察结果是否对miRNA编码基因也有效，我们使用表观遗传标记系统地鉴定了已知miRNA基因的启动子，并使用深度测序分析了它们的表达模式。我们发现染色质修饰也可以平衡miRNA编码基因。我们的数据表明，miRNA和蛋白质编码基因有着相似的染色质修饰调控机制，这使得诱导基因在环境刺激下激活。
Chromatin modifications have been implicated in the regulation of gene expression. While association of certain modifications with expressed or silent genes has been established, it remains unclear how changes in chromatin environment relate to changes in gene expression. In this article, we used ChIP-seq (chromatin immunoprecipitation with massively parallel sequencing) to analyze the genome-wide changes in chromatin modifications during activation of total human CD4(+) T cells by T-cell receptor (TCR) signaling. Surprisingly, we found that the chromatin modification patterns at many induced and silenced genes are relatively stable during the short-term activation of resting T cells. Active chromatin modifications were already in place for a majority of inducible protein-coding genes, even while the genes were silent in resting cells. Similarly, genes that were silenced upon T-cell activation retained positive chromatin modifications even after being silenced. To investigate if these observations are also valid for miRNA-coding genes, we systematically identified promoters for known miRNA genes using epigenetic marks and profiled their expression patterns using deep sequencing. We found that chromatin modifications can poise miRNA-coding genes as well. Our data suggest that miRNA-and protein-coding genes share similar mechanisms of regulation by chromatin modifications, which poise inducible genes for activation in response to environmental stimuli.