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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.

Titel:	Suz12 is essential for mouse development and for EZH2 histone methyltransferase activity.
Autor/in / Beteiligte Person:	Pasini, D ; Bracken, AP ; Jensen, MR ; Lazzerini Denchi, E ; Helin, K
Zeitschrift:	The EMBO journal, Jg. 23 (2004-10-13), Heft 20, S. 4061-71
Veröffentlichung:	2024- : [London] : Nature Publishing Group ; <i>Original Publication</i>: Eynsham, Oxford, England : Published for the European Molecular Biology Organization by IRL Press, [c1982-, 2004
Medientyp:	academicJournal
ISSN:	0261-4189 (print)
DOI:	10.1038/sj.emboj.7600402
Schlagwort:	Animals Carrier Proteins genetics Cell Division Cell Line, Tumor Cells, Cultured DNA-Binding Proteins Enhancer of Zeste Homolog 2 Protein Gene Expression Regulation, Developmental HeLa Cells Histone Methyltransferases Humans Methylation Mice Mice, Knockout Neoplasm Proteins Nuclear Proteins Polycomb Repressive Complex 2 Protein Methyltransferases Protein Structure, Tertiary Proteins chemistry Stem Cells metabolism Transcription Factors Carrier Proteins metabolism Embryonic Development Histone-Lysine N-Methyltransferase metabolism Proteins metabolism Repressor Proteins genetics
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [EMBO J] 2004 Oct 13; Vol. 23 (20), pp. 4061-71. <i>Date of Electronic Publication: </i>2004 Sep 23. MeSH Terms: Embryonic Development* ; Carrier Proteins / metabolism ; Histone-Lysine N-Methyltransferase / metabolism ; Proteins / metabolism ; Repressor Proteins / genetics ; Animals ; Carrier Proteins / genetics ; Cell Division ; Cell Line, Tumor ; Cells, Cultured ; DNA-Binding Proteins ; Enhancer of Zeste Homolog 2 Protein ; Gene Expression Regulation, Developmental ; HeLa Cells ; Histone Methyltransferases ; Humans ; Methylation ; Mice ; Mice, Knockout ; Neoplasm Proteins ; Nuclear Proteins ; Polycomb Repressive Complex 2 ; Protein Methyltransferases ; Protein Structure, Tertiary ; Proteins / chemistry ; Stem Cells / metabolism ; Transcription Factors References: Genes Dev. 2001 Feb 1;15(3):267-85. (PMID: 11159908) ; Development. 1998 Nov;125(22):4495-506. (PMID: 9778508) ; Proc Natl Acad Sci U S A. 2001 May 22;98(11):6348-53. (PMID: 11371647) ; Mol Cell Biol. 2001 Jul;21(13):4330-6. (PMID: 11390661) ; Science. 2001 Aug 10;293(5532):1074-80. (PMID: 11498575) ; Development. 2001 Sep;128(17):3371-9. (PMID: 11546753) ; Mol Cell Biol. 2001 Oct;21(20):6820-32. (PMID: 11564866) ; Biochim Biophys Acta. 2002 Jun 21;1602(2):151-61. (PMID: 12020801) ; Cancer Cell. 2002 Sep;2(3):243-7. (PMID: 12242156) ; Nature. 2002 Oct 10;419(6907):624-9. (PMID: 12374981) ; Cell. 2002 Oct 18;111(2):185-96. (PMID: 12408863) ; Cell. 2002 Oct 18;111(2):197-208. (PMID: 12408864) ; Science. 2002 Nov 1;298(5595):1039-43. (PMID: 12351676) ; Genes Dev. 2002 Nov 15;16(22):2893-905. (PMID: 12435631) ; Development. 2003 Sep;130(18):4235-48. (PMID: 12900441) ; Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11606-11. (PMID: 14500907) ; EMBO J. 2003 Oct 15;22(20):5323-35. (PMID: 14532106) ; Mol Cell. 2003 Dec;12(6):1577-89. (PMID: 14690609) ; J Biol Chem. 2004 Jan 2;279(1):401-6. (PMID: 14570930) ; Science. 2004 Jan 30;303(5658):644-9. (PMID: 14671313) ; Methods Enzymol. 2004;377:213-26. (PMID: 14979027) ; Mol Cell. 2004 Apr 23;14(2):183-93. (PMID: 15099518) ; Curr Opin Genet Dev. 2004 Apr;14(2):155-64. (PMID: 15196462) ; Cell Cycle. 2004 Apr;3(4):396-400. (PMID: 14752272) ; Genetics. 1990 Sep;126(1):185-99. (PMID: 1977656) ; Development. 1992 Feb;114(2):493-505. (PMID: 1350533) ; EMBO J. 1993 Apr;12(4):1513-22. (PMID: 8467801) ; Development. 1995 Feb;121(2):273-85. (PMID: 7768172) ; Cell Mol Life Sci. 1998 Jan;54(1):71-9. (PMID: 9487388) ; Curr Opin Genet Dev. 2001 Apr;11(2):175-81. (PMID: 11250141) Substance Nomenclature: 0 (Carrier Proteins) ; 0 (DNA-Binding Proteins) ; 0 (Neoplasm Proteins) ; 0 (Nuclear Proteins) ; 0 (Proteins) ; 0 (Repressor Proteins) ; 0 (SUZ12 protein, human) ; 0 (Suz12 protein, mouse) ; 0 (Transcription Factors) ; EC 2.1.1.- (Histone Methyltransferases) ; EC 2.1.1.- (Protein Methyltransferases) ; EC 2.1.1.43 (EZH2 protein, human) ; EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein) ; EC 2.1.1.43 (Ezh2 protein, mouse) ; EC 2.1.1.43 (Histone-Lysine N-Methyltransferase) ; EC 2.1.1.43 (Polycomb Repressive Complex 2) Entry Date(s): Date Created: 20040924 Date Completed: 20041221 Latest Revision: 20211203 Update Code: 20240513 PubMed Central ID: PMC524339

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Suz12 is essential for mouse development and for EZH2 histone methyltransferase activity.