Histone methyltransferase activity of a Drosophila Polycomb group repressor complex.
Polycomb group (PcG) proteins maintain transcriptional repression during development, likely by creating repressive chromatin states. The Extra Sex Combs (ESC) and Enhancer of Zeste [E(Z)] proteins are partners in an essential PcG complex, but its full composition and biochemical activities are not known. A SET domain in E(Z) suggests this complex might methylate histones. We purified an ESC-E(Z) complex from Drosophila embryos and found four major subunits: ESC, E(Z), NURF-55, and the PcG repressor, SU(Z)12. A recombinant complex reconstituted from these four subunits methylates lysine-27 of histone H3. Mutations in the E(Z) SET domain disrupt methyltransferase activity in vitro and HOX gene repression in vivo. These results identify E(Z) as a PcG protein with enzymatic activity and implicate histone methylation in PcG-mediated silencing.
Müller
Jürg
J
EMBL, Gene Expression Programme, Meyerhofstr. 1, 69117 Heidelberg, Germany. mueller@embl-heidelberg.de
Hart
Craig M
CM
Francis
Nicole J
NJ
Vargas
Marcus L
ML
Sengupta
Aditya
A
Wild
Brigitte
B
Miller
Ellen L
EL
O'Connor
Michael B
MB
Kingston
Robert E
RE
Simon
Jeffrey A
JA
D000818:Animals; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins / Q000235:genetics; D004330:Drosophila / Q000196:embryology / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D020868:Gene Silencing; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D018398:Homeodomain Proteins; D019476:Insect Proteins / Q000302:isolation & purification; D008239:Lysine / Q000378:metabolism; D008780:Methyltransferases / Q000378:metabolism*; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000302:isolation & purification / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D063151:Polycomb Repressive Complex 2; D011496:Protein Methyltransferases; D011995:Recombination, Genetic; D012097:Repressor Proteins / Q000302:isolation & purification / Q000378:metabolism*; D056505:Retinoblastoma-Binding Protein 4; D014157:Transcription Factors
C110251:Caf1-55 protein, Drosophila; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D019476:Insect Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; C066770:Pc protein, Drosophila; D012097:Repressor Proteins; D056505:Retinoblastoma-Binding Protein 4; C543390:Su(z)12 protein, Drosophila; D014157:Transcription Factors; C066177:Ubx protein, Drosophila; D000076983:Histone Methyltransferases; D008780:Methyltransferases; D011496:Protein Methyltransferases; 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