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Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans.

Greer EL, Maures TJ, Ucar D, Hauswirth AG, Mancini E, Lim JP, Benayoun BA, Shi Y, Brunet A - Nature (2011)

Bottom Line: Here we show that deficiencies in the H3K4me3 chromatin modifiers ASH-2, WDR-5 or SET-2 in the parental generation extend the lifespan of descendants up until the third generation.The transgenerational inheritance of lifespan extension by members of the ASH-2 complex is dependent on the H3K4me3 demethylase RBR-2, and requires the presence of a functioning germline in the descendants.Transgenerational inheritance of lifespan is specific for the H3K4me3 methylation complex and is associated with epigenetic changes in gene expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA.

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The transgenerational inheritance of longevity by deficiencies in ASH-2 complex members is dependent on the presence of the H3K4me3 demethylase RBR-2 and of an intact germlinea–b, Lifespan of genetically wildtype F3 descendents from wdr-5(ok1417) mutant worms (+/+ from P0 wdr-5 parents) in the presence of empty vector (control RNAi) (a) or rbr-2 RNAi (b). c–d, Lifespan of pgl-1 F3 descendents from a wdr-5(ok1417);pgl-1(bn101) mutant worms (pgl-1/pgl-1 from P0 wdr-5;pgl-1 parents) compared to descendents from pgl-1(bn101) worms at the permissive temperature (16°C) (c) and at the restrictive temperature (25°C) (d). Mean lifespan and statistics are presented in Supplementary Tables 3 and 4.
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Figure 4: The transgenerational inheritance of longevity by deficiencies in ASH-2 complex members is dependent on the presence of the H3K4me3 demethylase RBR-2 and of an intact germlinea–b, Lifespan of genetically wildtype F3 descendents from wdr-5(ok1417) mutant worms (+/+ from P0 wdr-5 parents) in the presence of empty vector (control RNAi) (a) or rbr-2 RNAi (b). c–d, Lifespan of pgl-1 F3 descendents from a wdr-5(ok1417);pgl-1(bn101) mutant worms (pgl-1/pgl-1 from P0 wdr-5;pgl-1 parents) compared to descendents from pgl-1(bn101) worms at the permissive temperature (16°C) (c) and at the restrictive temperature (25°C) (d). Mean lifespan and statistics are presented in Supplementary Tables 3 and 4.

Mentions: The H3K4me3 demethylase RBR-2 is necessary for the lifespan extension caused by deficiencies in members of the ASH-2 complex12. We asked if the transgenerational extension of longevity induced by deficiencies in members of the ASH-2 complex is dependent on RBR-2. The lifespan of genetically wildtype F3 descendents from P0 wdr-5 parents (+/+ from P0 wdr-5 parents) was no longer extended in the presence of rbr-2 RNAi (Fig. 4a, b). Similarly, F3 wildtype descendents from set-2;rbr-2 parents (+/+ from P0 set-2;rbr-2 parents) were no longer long-lived (Supplementary Fig. 1). Together, these data indicate that the transgenerational inheritance of longevity due to deficiencies in H3K4 trimethylation complex members is dependent on the H3K4me3 demethylase RBR-2. The fact that the longevity of wildtype descendents of wdr-5 and set-2 mutants is reverted by deficiencies in rbr-2 also suggests that this extended lifespan is unlikely to result from extraneous mutations in wdr-5 or set-2 strains. rbr-2 mutation or knock-down did not lead to a shortening of lifespan in descendents (Supplementary Fig. 2), indicating that by itself, RBR-2 deficiency does not affect longevity in a transgenerational manner.


Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans.

Greer EL, Maures TJ, Ucar D, Hauswirth AG, Mancini E, Lim JP, Benayoun BA, Shi Y, Brunet A - Nature (2011)

The transgenerational inheritance of longevity by deficiencies in ASH-2 complex members is dependent on the presence of the H3K4me3 demethylase RBR-2 and of an intact germlinea–b, Lifespan of genetically wildtype F3 descendents from wdr-5(ok1417) mutant worms (+/+ from P0 wdr-5 parents) in the presence of empty vector (control RNAi) (a) or rbr-2 RNAi (b). c–d, Lifespan of pgl-1 F3 descendents from a wdr-5(ok1417);pgl-1(bn101) mutant worms (pgl-1/pgl-1 from P0 wdr-5;pgl-1 parents) compared to descendents from pgl-1(bn101) worms at the permissive temperature (16°C) (c) and at the restrictive temperature (25°C) (d). Mean lifespan and statistics are presented in Supplementary Tables 3 and 4.
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Related In: Results  -  Collection

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Figure 4: The transgenerational inheritance of longevity by deficiencies in ASH-2 complex members is dependent on the presence of the H3K4me3 demethylase RBR-2 and of an intact germlinea–b, Lifespan of genetically wildtype F3 descendents from wdr-5(ok1417) mutant worms (+/+ from P0 wdr-5 parents) in the presence of empty vector (control RNAi) (a) or rbr-2 RNAi (b). c–d, Lifespan of pgl-1 F3 descendents from a wdr-5(ok1417);pgl-1(bn101) mutant worms (pgl-1/pgl-1 from P0 wdr-5;pgl-1 parents) compared to descendents from pgl-1(bn101) worms at the permissive temperature (16°C) (c) and at the restrictive temperature (25°C) (d). Mean lifespan and statistics are presented in Supplementary Tables 3 and 4.
Mentions: The H3K4me3 demethylase RBR-2 is necessary for the lifespan extension caused by deficiencies in members of the ASH-2 complex12. We asked if the transgenerational extension of longevity induced by deficiencies in members of the ASH-2 complex is dependent on RBR-2. The lifespan of genetically wildtype F3 descendents from P0 wdr-5 parents (+/+ from P0 wdr-5 parents) was no longer extended in the presence of rbr-2 RNAi (Fig. 4a, b). Similarly, F3 wildtype descendents from set-2;rbr-2 parents (+/+ from P0 set-2;rbr-2 parents) were no longer long-lived (Supplementary Fig. 1). Together, these data indicate that the transgenerational inheritance of longevity due to deficiencies in H3K4 trimethylation complex members is dependent on the H3K4me3 demethylase RBR-2. The fact that the longevity of wildtype descendents of wdr-5 and set-2 mutants is reverted by deficiencies in rbr-2 also suggests that this extended lifespan is unlikely to result from extraneous mutations in wdr-5 or set-2 strains. rbr-2 mutation or knock-down did not lead to a shortening of lifespan in descendents (Supplementary Fig. 2), indicating that by itself, RBR-2 deficiency does not affect longevity in a transgenerational manner.

Bottom Line: Here we show that deficiencies in the H3K4me3 chromatin modifiers ASH-2, WDR-5 or SET-2 in the parental generation extend the lifespan of descendants up until the third generation.The transgenerational inheritance of lifespan extension by members of the ASH-2 complex is dependent on the H3K4me3 demethylase RBR-2, and requires the presence of a functioning germline in the descendants.Transgenerational inheritance of lifespan is specific for the H3K4me3 methylation complex and is associated with epigenetic changes in gene expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA.

Show MeSH