Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells.
Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells.
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DOI：
10.1016/j.cell.2008.07.020
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发表时间：
2008-08-08
期刊：
影响因子：
64.5
通讯作者：
Young RA
中科院分区：
文献类型：
--
作者：
Marson A;Levine SS;Cole MF;Frampton GM;Brambrink T;Johnstone S;Guenther MG;Johnston WK;Wernig M;Newman J;Calabrese JM;Dennis LM;Volkert TL;Gupta S;Love J;Hannett N;Sharp PA;Bartel DP;Jaenisch R;Young RA
微小RNA（miRNAs）对正常胚胎干细胞（ES细胞）的自我更新和细胞分化至关重要，但ES细胞的关键转录调节因子如何控制miRNA基因表达尚未明确。在此，我们描述了一种新的ES细胞转录调控回路图谱，它包含蛋白质编码基因和miRNA基因，并且基于高分辨率的染色质免疫沉淀测序（ChIP - seq）数据、miRNA启动子的系统性鉴定以及多种细胞类型中短转录本的定量测序。我们发现，关键的ES细胞转录因子与大多数在ES细胞中优先表达的miRNAs的启动子以及一组沉默的miRNA基因的启动子相关联。这组沉默的miRNA基因在ES细胞中被多梳蛋白家族（Polycomb Group）共同占据，并在分化细胞中以组织特异性方式表达。这些数据揭示了关键的ES细胞转录因子如何促进有助于正常自我更新和细胞分化的miRNA表达程序，并将miRNAs及其靶标整合到一个扩展的控制ES细胞特性的调控回路模型中。
MicroRNAs (miRNAs) are crucial for normal embryonic stem (ES) cell self-renewal and cellular differentiation, but how miRNA gene expression is controlled by the key transcriptional regulators of ES cells has not been established. We describe here a new map of the transcriptional regulatory circuitry of ES cells that incorporates both protein-coding and miRNA genes, and which is based on high-resolution ChIP-seq data, systematic identification of miRNA promoters, and quantitative sequencing of short transcripts in multiple cell types. We find that the key ES cell transcription factors are associated with promoters for most miRNAs that are preferentially expressed in ES cells and with promoters for a set of silent miRNA genes. This silent set of miRNA genes is co-occupied by Polycomb Group proteins in ES cells and expressed in a tissue-specific fashion in differentiated cells. These data reveal how key ES cell transcription factors promote the miRNA expression program that contributes to normal self-renewal and cellular differentiation, and integrate miRNAs and their targets into an expanded model of the regulatory circuitry controlling ES cell identity.
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影响因子：
10.5
作者：
Cole, Megan F.;Johnstone, Sarah E.;Young, Richard A.
通讯作者：
Young, Richard A.
影响因子：
64.5
作者：
Guenther, Matthew G.;Levine, Stuart S.;Young, Richard A.
通讯作者：
Young, Richard A.
影响因子：
64.5
作者：
Kim, Jonghwan;Chu, Jianlin;Orkin, Stuart H.
通讯作者：
Orkin, Stuart H.
影响因子：
21.3
作者：
Jiang, Jianming;Chan, Yun-Shen;Ng, Huck-Hui
通讯作者：
Ng, Huck-Hui
影响因子：
56.9
作者：
Farh, KKH;Grimson, A;Bartel, DP
通讯作者：
Bartel, DP