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【分享】連接miRNA到胚胎干細(xì)胞的核心轉(zhuǎn)錄調(diào)控環(huán) 已有4人參與
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Connecting microRNA Genes to the Core Transcriptional Regulatory Circuitry of Embryonic Stem Cells 連接miRNA到胚胎干細(xì)胞的核心轉(zhuǎn)錄調(diào)控環(huán) 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著重要作用,然而調(diào)控的及調(diào)控機理并不明確。本文構(gòu)建了的轉(zhuǎn)錄調(diào)控環(huán),包括編碼基因和。基于高通量的數(shù)據(jù),系統(tǒng)地識別的啟動子,并且定量測序多個細(xì)胞類型中的短轉(zhuǎn)錄本,發(fā)現(xiàn)細(xì)胞中關(guān)鍵的調(diào)控子與細(xì)胞中表達(dá)的的啟動子相關(guān),并且與靶基因的啟動子相關(guān)。細(xì)胞中,這一組沉默的靶基因與蛋白共發(fā)生,并在不用的分化細(xì)胞中顯示組織特異性表達(dá)。這些數(shù)據(jù)揭示了關(guān)鍵細(xì)胞中促進(jìn)細(xì)胞表達(dá)過程的機理,并將這些整合到細(xì)胞的調(diào)控環(huán)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. 更多資料請查看www.bioknow.cn |
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