Polycomb-like 2 Associates with PRC2 and Regulates Transcriptional Networks during Mouse Embryonic Stem Cell Self-Renewal and Differentiation.

Authors

Emily Walker, University of Toronto
Wing Y. Chang, University of Toronto
Julie Hunkapiller, University of California - San Francisco
Gerard Cagney, University of California - San Francisco
Kamal Garcha, University of Toronto
Joseph Torchia, The University of Western Ontario
Nevan J. Krogan, University of California - San Francisco
Jeremy F. Reiter, University of California - San Francisco
William L. Stanford, University of Toronto

Document Type

Article

Publication Date

2-5-2010

Journal

Cell Stem Cell

Volume

6

Issue

2

First Page

153

Last Page

166

URL with Digital Object Identifier

http://dx.doi.org/10.1016/j.stem.2009.12.014

Abstract

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 pluripotency 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.