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Molecular and Cellular Biology, July 2001, p. 4330-4336, Vol. 21, No. 13
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.13.4330-4336.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

The Polycomb-Group Gene Ezh2 Is Required for Early Mouse Development

Dónal O'Carroll,1 Sylvia Erhardt,2 Michaela Pagani,1 Sheila C. Barton,2 M. Azim Surani,2 and Thomas Jenuwein1,*

Research Institute of Molecular Pathology (IMP), A-1030 Vienna, Austria,1 and Wellcome/CRC Institute of Cancer and Developmental Biology, Cambridge CB21QR, United Kingdom2

Received 22 December 2000/Returned for modification 1 February 2001/Accepted 28 March 2001

Polycomb-group (Pc-G) genes are required for the stable repression of the homeotic selector genes and other developmentally regulated genes, presumably through the modulation of chromatin domains. Among the Drosophila Pc-G genes, Enhancer of zeste [E(z)] merits special consideration since it represents one of the Pc-G genes most conserved through evolution. In addition, the E(Z) protein family contains the SET domain, which has recently been linked with histone methyltransferase (HMTase) activity. Although E(Z)-related proteins have not (yet) been directly associated with HMTase activity, mammalian Ezh2 is a member of a histone deacetylase complex. To investigate its in vivo function, we generated mice deficient for Ezh2. The Ezh2 null mutation results in lethality at early stages of mouse development. Ezh2 mutant mice either cease developing after implantation or initiate but fail to complete gastrulation. Moreover, Ezh2-deficient blastocysts display an impaired potential for outgrowth, preventing the establishment of Ezh2-null embryonic stem cells. Interestingly, Ezh2 is up-regulated upon fertilization and remains highly expressed at the preimplantation stages of mouse development. Together, these data suggest an essential role for Ezh2 during early mouse development and genetically link Ezh2 with eed and YY1, the only other early-acting Pc-G genes.

* Corresponding author. Mailing address: Research Institute for Molecular Pathology, Dr. Bohrgasse 7, A-1030 Vienna, Austria. Phone: (43/1) 797-30-474. Fax: (43/1) 798-7153. E-mail: jenuwein{at}nt.imp.univie.ac.at.

Molecular and Cellular Biology, July 2001, p. 4330-4336, Vol. 21, No. 13
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.13.4330-4336.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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