Characterization of the grappa gene, the Drosophila histone H3 lysine 79 methyltransferase.
We have identified a novel gene named grappa (gpp) that is the Drosophila ortholog of the Saccharomyces cerevisiae gene Dot1, a histone methyltransferase that modifies the lysine (K)79 residue of histone H3. gpp is an essential gene identified in a genetic screen for dominant suppressors of pairing-dependent silencing, a Polycomb-group (Pc-G)-mediated silencing mechanism necessary for the maintenance phase of Bithorax complex (BX-C) expression. Surprisingly, gpp mutants not only exhibit Pc-G phenotypes, but also display phenotypes characteristic of trithorax-group mutants. Mutations in gpp also disrupt telomeric silencing but do not affect centric heterochromatin. These apparent contradictory phenotypes may result from loss of gpp activity in mutants at sites of both active and inactive chromatin domains. Unlike the early histone H3 K4 and K9 methylation patterns, the appearance of methylated K79 during embryogenesis coincides with the maintenance phase of BX-C expression, suggesting that there is a unique role for this chromatin modification in development.
Shanower
Gregory A
GA
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Muller
Martin
M
Blanton
Jason L
JL
Honti
Viktor
V
Gyurkovics
Henrik
H
Schedl
Paul
P
D000818:Animals; D029721:Drosophila Proteins / Q000502:physiology; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D047108:Embryonic Development; D005260:Female; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D005799:Genes, Dominant; D006570:Heterochromatin / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D018398:Homeodomain Proteins / Q000502:physiology; D008239:Lysine / Q000378:metabolism; D008297:Male; D008745:Methylation; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000737:chemistry; D010641:Phenotype; D063150:Polycomb Repressive Complex 1; D012097:Repressor Proteins / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry; D016615:Telomere / Q000378:metabolism*
D029721:Drosophila Proteins; D006570:Heterochromatin; D006657:Histones; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; C066770:Pc protein, Drosophila; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C416235:Dot1 protein, S cerevisiae; D011495:Histone-Lysine N-Methyltransferase; D063150:Polycomb Repressive Complex 1; D008239:Lysine