Central role of Drosophila SU(VAR)3-9 in histone H3-K9 methylation and heterochromatic gene silencing.
Su(var)3-9 is a dominant modifier of heterochromatin-induced gene silencing. Like its mammalian and Schizosaccharomyces pombe homologues, Su(var) 3-9 encodes a histone methyltransferase (HMTase), which selectively methylates histone H3 at lysine 9 (H3-K9). In Su(var)3-9 null mutants, H3-K9 methylation at chromocentre heterochromatin is strongly reduced, indicating that SU(VAR)3-9 is the major heterochromatin-specific HMTase in Drosophila. SU (VAR)3-9 interacts with the heterochromatin-associated HP1 protein and with another silencing factor, SU(VAR)3-7. Notably, SU(VAR)3-9-HP1 interaction is interdependent and governs distinct localization patterns of both proteins. In Su(var)3-9 null mutants, concentration of HP1 at the chromocentre is nearly lost without affecting HP1 accumulation at the fourth chromosome. By contrast, in HP1 null mutants SU(VAR)3-9 is no longer restricted at heterochromatin but broadly dispersed across the chromosomes. Despite this interdependence, Su(var)3-9 dominates the PEV modifier effects of HP1 and Su(var)3-7 and is also epistatic to the Y chromosome effect on PEV. Finally, the human SUV39H1 gene is able to partially rescue Su(var)3-9 silencing defects. Together, these data indicate a central role for the SU(VAR)3-9 HMTase in heterochromatin-induced gene silencing in Drosophila.
Schotta
Gunnar
G
Institute of Genetics, Biologicum, Martin Luther University Halle, Weinbergweg 10, D-06120 Halle, Germany.
Ebert
Anja
A
Krauss
Veiko
V
Fischer
Andreas
A
Hoffmann
Jan
J
Rea
Stephen
S
Jenuwein
Thomas
T
Dorn
Rainer
R
Reuter
Gunter
G
D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics*; D004843:Epistasis, Genetic; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D020868:Gene Silencing / Q000502:physiology*; D005816:Genetic Complementation Test; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000502:physiology*; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D013045:Species Specificity; D014998:Y Chromosome / Q000235:genetics
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006570:Heterochromatin; D006657:Histones; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C449619:Su(var)3-7 protein, Drosophila; C089148:Su(var)3-9 protein, Drosophila; C452193:heterochromatin protein 1, Drosophila; C407843:SUV39H1 protein, human; D008780:Methyltransferases