Emily Walker, Janet L Manias, Wing Y Chang, William L Stanford
Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
Cell cycle (Georgetown, Tex.) 2011 Jan 1Recent 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.
Emily Walker, Janet L Manias, Wing Y Chang, William L Stanford. PCL2 modulates gene regulatory networks controlling self-renewal and commitment in embryonic stem cells. Cell cycle (Georgetown, Tex.). 2011 Jan 1;10(1):45-51
PMID: 21193838
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