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Molecular and Cellular Biology, August 2005, p. 6857-6868, Vol. 25, No. 16
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.16.6857-6868.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Subunit Contributions to Histone Methyltransferase Activities of Fly and Worm Polycomb Group Complexes

Carrie S. Ketel,1 Erica F. Andersen,1 Marcus L. Vargas,1 Jinkyo Suh,2 Susan Strome,2 and Jeffrey A. Simon1*

Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455,1 Department of Biology, Indiana University, Bloomington, Indiana 474052

Received 6 April 2005/ Returned for modification 6 May 2005/ Accepted 25 May 2005

The ESC-E(Z) complex of Drosophila melanogaster Polycomb group (PcG) repressors is a histone H3 methyltransferase (HMTase). This complex silences fly Hox genes, and related HMTases control germ line development in worms, flowering in plants, and X inactivation in mammals. The fly complex contains a catalytic SET domain subunit, E(Z), plus three noncatalytic subunits, SU(Z)12, ESC, and NURF-55. The four-subunit complex is >1,000-fold more active than E(Z) alone. Here we show that ESC and SU(Z)12 play key roles in potentiating E(Z) HMTase activity. We also show that loss of ESC disrupts global methylation of histone H3-lysine 27 in fly embryos. Subunit mutations identify domains required for catalytic activity and/or binding to specific partners. We describe missense mutations in surface loops of ESC, in the CXC domain of E(Z), and in the conserved VEFS domain of SU(Z)12, which each disrupt HMTase activity but preserve complex assembly. Thus, the E(Z) SET domain requires multiple partner inputs to produce active HMTase. We also find that a recombinant worm complex containing the E(Z) homolog, MES-2, has robust HMTase activity, which depends upon both MES-6, an ESC homolog, and MES-3, a pioneer protein. Thus, although the fly and mammalian PcG complexes absolutely require SU(Z)12, the worm complex generates HMTase activity from a distinct partner set.


* Corresponding author. Mailing address: University of Minnesota, Department of Genetics, Cell Biology and Development, 321 Church St. SE, Minneapolis, MN 55455. Phone: (612) 626-5097. Fax: (612) 626-6140. E-mail: simon{at}cbs.umn.edu.


Molecular and Cellular Biology, August 2005, p. 6857-6868, Vol. 25, No. 16
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.16.6857-6868.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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