期刊
CELL CYCLE
卷 10, 期 1, 页码 45-51出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.10.1.14389
关键词
polycomb-like 2; jarid2; polycomb; embryonic stem cell; gene regulatory network; histone methylation
类别
资金
- Canadian Cancer Society Research Institute [19122]
- CIHR
- Heart & Stroke Foundation of Canada
- Canada Research Chair
Recent reports have better elucidated the components of the Polycomb Repressive Complex 2 (PRC2) and its functional role in embryonic stem cells (ESCs) and their differentiated derivatives. The depletion of a newly described mammalian PRC2 associated protein, PCL2, leads to an increase in ESC self-renewal and a delay in differentiation, a phenotype similar to knockouts of the core PRC2 members. Genomic and cell biology data suggest that PCL2 is important in cell fate decisions and may play a role in recruitment of PRC2 to target genes and histone methylation. Importantly, depletion of PCL2 in ESCs leads to a decrease in 3meH3K27 at the proximal promoter regions of pluripotency transcription factors Tbx3, Klf4, Foxd3 and a concomitant increase in gene expression. These proteins subsequently activate expression of Oct4, Nanog and Sox2 through a feed-forward gene regulatory circuit, altering the core pluripotency network and driving cell fate decisions towards self-renewal. We propose a model whereby alteration of the epigenetic state of Tbx3, Klf4 and Foxd3 results in the enforced expression of the pluripotency network, preventing differentiation.
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