Polycomb group suppressor of zeste 12 links heterochromatin protein 1alpha and enhancer of zeste 2.
Drosophila suppressor of zeste 12 (Su(z)12) is a Polycomb group (PcG) transcriptional repressor and is present in E(z)-ESC, a multiprotein complex with methylation activity specific for lysine 9 and 27 of histone H3. Although 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), the 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 the zinc finger motif and the VEFS (VRN2-EMF2-FIS2-Su(z)12) box for HP1alpha (amino acid residues 479-536) and the VEFS box for EZH2 (amino acid residues 600-639), which are not mutually exclusive. Interestingly this region of the VEFS box has been shown to be critical for the 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.
Yamamoto
Ken
K
Division of Molecular Population Genetics, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. kyama@bioreg.kyushu-u.ac.jp
Sonoda
Miki
M
Inokuchi
Junichi
J
Shirasawa
Senji
S
Sasazuki
Takehiko
T
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002522:Chlorocebus aethiops; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone; D003001:Cloning, Molecular; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D006570:Heterochromatin / Q000737:chemistry / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry; D063150:Polycomb Repressive Complex 1; D063151:Polycomb Repressive Complex 2; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D016335:Zinc Fingers
C000715594:CBX5 protein, human; D002352:Carrier Proteins; D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins; D006570:Heterochromatin; D006657:Histones; D009687:Nuclear Proteins; C066770:Pc protein, Drosophila; D010446:Peptide Fragments; D011994:Recombinant Proteins; D012097:Repressor Proteins; C543390:Su(z)12 protein, Drosophila; D000090266:Chromobox Protein Homolog 5; C083329:E(z) protein, Drosophila; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2; C543389:esc protein, Drosophila; D063150:Polycomb Repressive Complex 1; D008239:Lysine