期刊
CELL STEM CELL
卷 6, 期 2, 页码 153-166出版社
CELL PRESS
DOI: 10.1016/j.stem.2009.12.014
关键词
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资金
- CIHR [MOP-74528]
- Canadian Cancer Society [19122]
- NIH [RO1AR054396]
- CIRM [RN2-00919]
- Burroughs Wellcome Fund
- Packard Foundation
- Sandler Family Supporting Foundation
- Keck Foundation
- Searle Foundation
- Ontario Graduate Studentship in Science and Technology
- MRI
- Canada Research Chair
- NCIC
Polycomb group (PcG) proteins are conserved epigenetic transcriptional repressors that control numerous developmental gene expression programs and have recently been implicated in modulating embryonic stem cell (ESC) fate. We identified the PcG protein PCL2 (polycomb-like 2) in a genome-wide screen for regulators of self-renewal and pluri-potency and predicted that it would play an important role in mouse ESC-fate determination. Using multiple biochemical strategies, we provide evidence that PCL2 is a Polycomb Repressive Complex 2 (PRC2)-associated protein in mouse ESCs. Knockdown of Pcl2 in ESCs resulted in heightened self-renewal characteristics, defects in differentiation, and altered patterns of histone methylation. Integration of global gene expression and promoter occupancy analyses allowed us to identify PCL2 and PRC2 transcriptional targets and draft regulatory networks. We describe the role of PCL2 in both modulating transcription of ESC self-renewal genes in undifferentiated ESCs as well as developmental regulators during early commitment and differentiation.
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