Pasini D, Bracken AP, Jensen MR et al.Suz12 is essential for mouse development and for EZH2 histone methyltransferase activity. EMBO J 23:4061-4071

European Institute of Oncology, Milan, Italy.
The EMBO Journal (Impact Factor: 10.43). 11/2004; 23(20):4061-71. DOI: 10.1038/sj.emboj.7600402
Source: PubMed


SUZ12 is a recently identified Polycomb group (PcG) protein, which together with EZH2 and EED forms different Polycomb repressive complexes (PRC2/3). These complexes contain histone H3 lysine (K) 27/9 and histone H1 K26 methyltransferase activity specified by the EZH2 SET domain. Here we show that mice lacking Suz12, like Ezh2 and Eed mutant mice, are not viable and die during early postimplantation stages displaying severe developmental and proliferative defects. Consistent with this, we demonstrate that SUZ12 is required for proliferation of cells in tissue culture. Furthermore, we demonstrate that SUZ12 is essential for the activity and stability of the PRC2/3 complexes in mouse embryos, in tissue culture cells and in vitro. Strikingly, Suz12-deficient embryos show a specific loss of di- and trimethylated H3K27, demonstrating that Suz12 is indeed essential for EZH2 activity in vivo. In conclusion, our data demonstrate an essential role of SUZ12 in regulating the activity of the PRC2/3 complexes, which are required for regulating proliferation and embryogenesis.

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    • "Interestingly, knockdown of any single PRC2 component produced similar phenotypes, suggesting that all three proteins need to be present for normal PRC2 activity. This result was consistent with previous reports that all three core proteins are required for functional assembly of PRC2 (Cao and Zhang, 2004; Pasini et al., 2004; Montgomery et al., 2005). Based on this observation, we focused on EZH2 only in the subsequent studies. "
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    • "RING1A, RING1B, and BMI1 are core PRC1 members while SUZ12, EZH2, and EED form core PRC2 members (de Napoles et al., 2004; Surface et al., 2010). Knockout studies of PcG proteins have established their importance during in vivo development (Voncken et al., 2003; Pasini et al., 2004) but their role in lineage specification and differentiation in vitro remains to be completely elucidated. Most studies have shown localization of PcG mediated histone modification (H3K27me3) during differentiation in mouse ES cells (Boyer et al., 2006; Lee et al., 2006; Pasini et al., 2007), while some have shown histone modifications catalyzed by PcG proteins during differentiation into a specific lineage (Hawkins et al., 2010; Xie et al., 2013). "
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    ABSTRACT: Human embryonic (hES) stem cells are excellent model to study lineage specification and differentiation into various cell types. Differentiation necessitates repression of specific genes not required for a particular lineage. Polycomb Group (PcG) proteins are key histone modifiers, whose primary function is gene repression. PcG proteins form complexes called Polycomb Repressive Complexes (PRCs), which catalyze histone modifications such as H2AK119ub1, H3K27me3 and H3K9me3. PcG proteins play a crucial role during differentiation of stem cells. The expression of PcG transcripts during differentiation of hES cells into endoderm, mesoderm and ectoderm lineage is yet to be shown. In-house derived hES cell line KIND1 was differentiated into endoderm, mesoderm and ectoderm lineages; followed by characterized using RT-PCR for HNF4A, CDX2, MEF2C, TBX5, SOX1 and MAP2. qRT-PCR and western blotting was performed to compare expression of PcG transcripts and proteins across all the three lineages. We observed that cells differentiated into endoderm showed upregulation of RING1B, BMI1, EZH2 and EED transcripts. Mesoderm differentiation was characterized by significant downregulation of all PcG transcripts during later stages. BMI1 and RING1B were upregulated while EZH2, SUZ12 and EED remained low during ectoderm differentiation. Western Blotting also showed distinct expression of BMI1 and EZH2 during differentiation into three germ layers. Our study shows that hES cells differentiating into endoderm, mesoderm and ectoderm lineages show distinct PcG expression profile at transcript and protein level. This article is protected by copyright. All rights reserved.
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    • "Numerous genes have been implicated in the genesis and development of RB (2). Suppressor of Zeste 12 homolog (SUZ12), is an important component of polycomb group protein (PcG), and is essential in cell proliferation, cell cycle and embryonic development processes (3,4). SUZ12 is also known to regulate tumor phenotype through altering gene expression, with an important regulatory role in tumor genesis and development, and this has been widely investigated (5). "
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