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Papers In Press, published online ahead of print October 21, 2003
J. Biol. Chem, 10.1074/jbc.M307344200
Submitted on July 9, 2003
Revised on October 21, 2003
Accepted on October 21, 2003

Polycomb group, suppressor of Zeste 12, links heterochromatin protein 1alpha and enhancer of Zeste 2

Ken Yamamoto, Miki Sonoda, Junichi Inokuchi, Senji Shirasawa, and Takehiko Sasazuki

Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582

Corresponding Author: kyama{at}bioreg.kyushu-u.ac.jp

Drosophila suppressor of zeste-12 [Su(z)12] is Polycomb group (PcG) transcriptional repressor and is present in a E(z)-ESC, a multiprotein complex with methylation activity specific for lysine 9 and 27 of histone H3. Although a PcG- and heterochromatin-mediated gene silencing have been considered distinct, mutant flies of Su(z)12 showed not only homeotic transformation but also position effect variegation. We now report that the mammalian SU(Z)12 directly interacts with heterochromatin protein 1alpha (HP1alpha ) and PcG Enhancer of Zeste 2 (EZH2), mammalian counterpart of E(z), in vitro and in vivo. Two distinct domains in SU(Z)12 are involved in these interactions, the region between zinc-finger motif and VEFS [VRN2-EMF2-FIS2-Su(z)12] box for HP1alpha (amino acid residues 479-536) and VEFS box for EZH2 (amino acid residues 600-639), which are not mutually exclusive. Interestingly this region of VEFS box has been shown to be critical for phenotype of the Su(z)12 mutant fly. In addition SU(Z)12 represses transcription activity in the presence of HP1alpha in a reporter assay. These results provide a molecular explanation for the functional link of these epigenetic silencing processes mediated by SU(Z)12.


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