Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms

By R. Margueron, Guohong Li, K. Sarma, A. Blais, Jiri Zavadil, C. Woodcock, B. Dynlacht, D. Reinberg. Molecules and Cells, 2008

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Polycomb group proteins are critical to maintaining gene repression established during Drosophila development. Part of this group forms the PRC2 complex containing Ez that catalyzes methylation of histone H3 lysine 27 (H3K37me2/3), marks repressive to transcription. We report that the mammalian homologs Ezh1 and Ezh2 form similar PRC2 complexes but exhibit contrasting repressive roles. While PRC2-Ezh2 catalyzes H3K27me2/3 and its knockdown affects global H3K27me2/3 levels, PRC2-Ezh1 performs this function weakly. In accordance, Ezh1 knockdown was ineffectual on global H3K27me2/3 levels. Instead, PRC2-Ezh1 directly and robustly represses transcription from chromatinized templates and compacts chromatin in the absence of the methyltransferase cofactor SAM, as evidenced by electron microscopy. Ezh1 targets a subset of Ezh2 genes, yet Ezh1 is more abundant in non-proliferative adult organs while Ezh2 expression is tightly associated with proliferation as evidenced when analyzing aging mouse kidney. These results might reflect sub-functionalization of a PcG protein during evolution.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/e181ca5a0fc12491a994bb0dd66e944161aada5f

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Citations in the corpus

Ezh2 Orchestrates Gene Expression for the Stepwise Differentiation of Tissue-Specific Stem Cells (2009, background): “Ezh1 Increases in the Epidermis as Ezh2 Wanes: Partially Overlapping Activities of Ezh2 and Ezh1 Whereas Ezh2 is often expressed during embryogenesis, Ezh1 is found in adult tissues (Laible et al., 1997; Margueron et al., 2008; Su et al., 2003).”
Mechanisms of Polycomb gene silencing: knowns and unknowns (2009, background): “Whereas EZH2 is highly expressed during embryogenesis and in proliferating cells, EZH1 predominates in adult tissues and non-dividing cell”
Genome Regulation by Polycomb and Trithorax: 70 Years and Counting. (2017, neutral): “Moreover, PRC2 itself can lead to chromatin compaction (Margueron et al., 2008; Terranova et al., 2008).”
Transcriptional regulation by Polycomb group proteins (2013, background): “; and from the Novo Nordisk Foundation, the Danish Cancer Society and the Danish Council for Strategic Research (12-110503) to K.”
Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders (2010, background): “Orkin (Howard Hughes Medical Institute, Boston, Massachusetts, USA”
The Polycomb Complex PRC2 and its Mark in Life (2011, background): “Also, PRC2 complexes containing EZH1 (PRC2–EZH1) in lieu of EZH2 have low methyltransferase activity compared with PRC2–EZH2 (ref”