Limits...
Heterochromatic genome stability requires regulators of histone H3 K9 methylation.

Peng JC, Karpen GH - PLoS Genet. (2009)

Bottom Line: Heterochromatin contains many repetitive DNA elements and few protein-encoding genes, yet it is essential for chromosome organization and inheritance.Similar effects of lower magnitude were observed in animals that lack the RNA interference pathway component Dcr2.These results suggest that the H3K9 methylation and RNAi pathways ensure heterochromatin stability.

View Article: PubMed Central - PubMed

Affiliation: Lawrence Berkeley National Laboratory, Department of Genome and Computational Biology, Berkeley, California, USA.

ABSTRACT
Heterochromatin contains many repetitive DNA elements and few protein-encoding genes, yet it is essential for chromosome organization and inheritance. Here, we show that Drosophila that lack the Su(var)3-9 H3K9 methyltransferase display significantly elevated frequencies of spontaneous DNA damage in heterochromatin, in both somatic and germ-line cells. Accumulated DNA damage in these mutants correlates with chromosomal defects, such as translocations and loss of heterozygosity. DNA repair and mitotic checkpoints are also activated in mutant animals and are required for their viability. Similar effects of lower magnitude were observed in animals that lack the RNA interference pathway component Dcr2. These results suggest that the H3K9 methylation and RNAi pathways ensure heterochromatin stability.

Show MeSH

Related in: MedlinePlus

Developmental progression and lifespan of wild type and Su(var)3-9 animals.A) Analysis of developmental progression for wild type and Su(var)3-9 animals. Animals in the two groups laid comparable numbers of eggs. In all three assays, the p values comparing Su(var)3-9 to wild type are <0.001 by Student's t test. n>150 for each genotype. B) The graph shows lifespan analysis of wild type and Su(var)3-9 adult female flies. Su(var)3-9 females displayed significantly shorter lifespan than wild type (p<0.01 by Wilcoxon signed rank test). n>50 female flies.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2654965&req=5

pgen-1000435-g004: Developmental progression and lifespan of wild type and Su(var)3-9 animals.A) Analysis of developmental progression for wild type and Su(var)3-9 animals. Animals in the two groups laid comparable numbers of eggs. In all three assays, the p values comparing Su(var)3-9 to wild type are <0.001 by Student's t test. n>150 for each genotype. B) The graph shows lifespan analysis of wild type and Su(var)3-9 adult female flies. Su(var)3-9 females displayed significantly shorter lifespan than wild type (p<0.01 by Wilcoxon signed rank test). n>50 female flies.

Mentions: Previous analysis showed that mice deleted for both Suv3-9 genes exhibit genome instability and partial prenatal lethality [42]. Surprisingly, despite elevated frequencies of DNA damage, chromosome rearrangements and LOH shown here, Su(var)3-9 mutant animals derived from mothers are homozygous viable and fertile [43]. However, our analysis of survival at various developmental stages showed significant differences between wild type and mutant animals (Figure 4A). Su(var)3-9 mutant parents produced 93% fertilized eggs, 72% of which hatch to embryos, compared to 94% hatching for wild type (Figure 4A). Defective development during embryogenesis is the likely cause of the lower hatch rates. Once they hatched into larvae, developmental timing and eclosion rates of Su(var)3-9 mutants were comparable to wild type. Thus, Su(var)3-9 mutant animals are mostly viable and fertile; larval and pupal development are normal, but they have elevated levels of unfertilized eggs and embryonic lethality compared to wild type. In addition, Su(var)3-9 females exhibit significantly shorter adult lifespans compared to wild type (Figure 4B, p<0.01).


Heterochromatic genome stability requires regulators of histone H3 K9 methylation.

Peng JC, Karpen GH - PLoS Genet. (2009)

Developmental progression and lifespan of wild type and Su(var)3-9 animals.A) Analysis of developmental progression for wild type and Su(var)3-9 animals. Animals in the two groups laid comparable numbers of eggs. In all three assays, the p values comparing Su(var)3-9 to wild type are <0.001 by Student's t test. n>150 for each genotype. B) The graph shows lifespan analysis of wild type and Su(var)3-9 adult female flies. Su(var)3-9 females displayed significantly shorter lifespan than wild type (p<0.01 by Wilcoxon signed rank test). n>50 female flies.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2654965&req=5

pgen-1000435-g004: Developmental progression and lifespan of wild type and Su(var)3-9 animals.A) Analysis of developmental progression for wild type and Su(var)3-9 animals. Animals in the two groups laid comparable numbers of eggs. In all three assays, the p values comparing Su(var)3-9 to wild type are <0.001 by Student's t test. n>150 for each genotype. B) The graph shows lifespan analysis of wild type and Su(var)3-9 adult female flies. Su(var)3-9 females displayed significantly shorter lifespan than wild type (p<0.01 by Wilcoxon signed rank test). n>50 female flies.
Mentions: Previous analysis showed that mice deleted for both Suv3-9 genes exhibit genome instability and partial prenatal lethality [42]. Surprisingly, despite elevated frequencies of DNA damage, chromosome rearrangements and LOH shown here, Su(var)3-9 mutant animals derived from mothers are homozygous viable and fertile [43]. However, our analysis of survival at various developmental stages showed significant differences between wild type and mutant animals (Figure 4A). Su(var)3-9 mutant parents produced 93% fertilized eggs, 72% of which hatch to embryos, compared to 94% hatching for wild type (Figure 4A). Defective development during embryogenesis is the likely cause of the lower hatch rates. Once they hatched into larvae, developmental timing and eclosion rates of Su(var)3-9 mutants were comparable to wild type. Thus, Su(var)3-9 mutant animals are mostly viable and fertile; larval and pupal development are normal, but they have elevated levels of unfertilized eggs and embryonic lethality compared to wild type. In addition, Su(var)3-9 females exhibit significantly shorter adult lifespans compared to wild type (Figure 4B, p<0.01).

Bottom Line: Heterochromatin contains many repetitive DNA elements and few protein-encoding genes, yet it is essential for chromosome organization and inheritance.Similar effects of lower magnitude were observed in animals that lack the RNA interference pathway component Dcr2.These results suggest that the H3K9 methylation and RNAi pathways ensure heterochromatin stability.

View Article: PubMed Central - PubMed

Affiliation: Lawrence Berkeley National Laboratory, Department of Genome and Computational Biology, Berkeley, California, USA.

ABSTRACT
Heterochromatin contains many repetitive DNA elements and few protein-encoding genes, yet it is essential for chromosome organization and inheritance. Here, we show that Drosophila that lack the Su(var)3-9 H3K9 methyltransferase display significantly elevated frequencies of spontaneous DNA damage in heterochromatin, in both somatic and germ-line cells. Accumulated DNA damage in these mutants correlates with chromosomal defects, such as translocations and loss of heterozygosity. DNA repair and mitotic checkpoints are also activated in mutant animals and are required for their viability. Similar effects of lower magnitude were observed in animals that lack the RNA interference pathway component Dcr2. These results suggest that the H3K9 methylation and RNAi pathways ensure heterochromatin stability.

Show MeSH
Related in: MedlinePlus