Transcriptomics,Genomics

Dataset Information

305

Regulation of pluripotency and self-renewal of ES cells through epigenetic-threshold modulation and mRNA pruning


ABSTRACT: The core pluripotency factors (Oct4, Sox2, and Nanog), the Myc network, and the chromatin-modifying complexes such as PRC2 ensure the pluripotency and self-renewal of ES cells (ESC). How these factors coordinate with one another remains poorly understood. We report that Utf1, a target of Oct4 and Sox2, is a new bivalent chromatin component that buffers poised states of bivalent genes. By limiting PRC2 loading and Histone 3 lysine-27 trimethylation, Utf1 sets proper activation thresholds for bivalent genes. It also promotes nuclear tagging of mRNAs transcribed from insufficiently silenced bivalent genes for cytoplasmic degradation through mRNA de-capping. Whereas these opposing functions of Utf1 allow proper execution of ESC pluripotency, the mRNA pruning function also ensures rapid cell proliferation by blocking the Myc-Arf feedback regulation. Thus, Utf1 is an important regulator that couples the core pluripotency factors with Myc and PRC2 networks to promote proliferation and pluripotency execution of ESCs. First we mapped Utf1 binding sites in ESCs using the biotin-mediated and cross-linked ChIP-sequencing. To investigate how Utf1 might regulate gene expression, we did RNA-seq on WT and Utf1-KO ES cells. Then we did ChIP-seq of Suz12 and H3K27me3 on WT and Utf1-KO ES cells to study whether Utf1 affects PRC2 loading and H3K27me3 modofication, using H3 as control. Finally, we did RNAseq on WT and Dcp1a-KD ES cells to confirm Utf1 repress gene expression by recruiting Dcp1a complex.

ORGANISM(S): Mus musculus  

SUBMITTER: Keji Zhao   Yixian Zheng  Gangqing Hu  Xiaobin Zheng  Junling Jia  Kairong Cui 

PROVIDER: E-GEOD-39513 | ArrayExpress | 2012-10-26

SECONDARY ACCESSION(S): SRP014645GSE39513PRJNA171100

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

Regulation of pluripotency and self- renewal of ESCs through epigenetic-threshold modulation and mRNA pruning.

Jia Junling J   Zheng Xiaobin X   Hu Gangqing G   Cui Kairong K   Zhang Junqi J   Zhang Anying A   Jiang Hao H   Lu Bingwen B   Yates John J   Liu Chengyu C   Zhao Keji K   Zheng Yixian Y  

Cell 20121001 3


Embryonic stem cell (ESC) pluripotency requires bivalent epigenetic modifications of key developmental genes regulated by various transcription factors and chromatin-modifying enzymes. How these factors coordinate with one another to maintain the bivalent chromatin state so that ESCs can undergo rapid self-renewal while retaining pluripotency is poorly understood. We report that Utf1, a target of Oct4 and Sox2, is a bivalent chromatin component that buffers poised states of bivalent genes. By li  ...[more]

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