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biomill8358

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注册: 2009-01-08

[交流] 【分享】连接miRNA到胚胎干细胞的核心转录调控环已有4人参与

Connecting microRNA Genes to the Core Transcriptional Regulatory Circuitry of Embryonic Stem Cells
连接miRNA到胚胎干细胞的核心转录调控环
AlexanderMarson,StuartS.Levine, MeganF.Cole, GarrettM.Frampton, TobiasBrambrink, SarahJohnstone, MatthewG.Guenther, WendyK.Johnston, MariusWernig, JamieNewman
摘要：miRNA在的自我更新和分化中起着重要作用，然而调控的及调控机理并不明确。本文构建了的转录调控环，包括编码基因和。基于高通量的数据，系统地识别的启动子，并且定量测序多个细胞类型中的短转录本，发现细胞中关键的调控子与细胞中表达的的启动子相关，并且与靶基因的启动子相关。细胞中，这一组沉默的靶基因与蛋白共发生，并在不用的分化细胞中显示组织特异性表达。这些数据揭示了关键细胞中促进细胞表达过程的机理，并将这些整合到细胞的调控环中。
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 the transcriptional regulatory circuitry of ES cells that incorporates protein-coding and miRNA genes 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 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 shows tissue-specific expression in differentiated cells. These data reveal how key ES cell transcription factors promote the ES cell miRNA expression program and integrate miRNAs into the regulatory circuitry controlling ES cell identity.
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