H3K4 demethylase activities repress proliferative and postmitotic aging

Alvares, Stacy M.; A., Mayberry, Gaea; Joyner, Ebony Y.; Lakowski, Bernard; Ahmed, Shawn

doi:10.1111/acel.12166

Cited by 46 publications

(44 citation statements)

References 49 publications

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“…A recent report (Alvares et al, 2013) suggested that spr-5(by134) mutant worms only displayed a transgenerational fertility defect at the elevated temperature of 25°C but not at 20°C. This result was contrary to the initial results reported by (Katz et al, 2009) as well as to our observations.…”

Section: Discussionmentioning

confidence: 99%

A Histone Methylation Network Regulates Transgenerational Epigenetic Memory in C. elegans

et al. 2014

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Summary How epigenetic information is transmitted from generation to generation remains largely unknown. Deletion of the C. elegans Histone H3 lysine 4 dimethyl (H3K4me2) demethylase spr-5 leads to inherited accumulation of the euchromatic H3K4me2 mark and progressive decline in fertility. Here we identified multiple chromatin-modifying factors, including novel H3K4me1/me2 and H3K9me3 methyltransferases, an H3K9me3 demethylase and an H3K9me reader, which either suppress or accelerate the progressive transgenerational phenotypes of spr-5 mutant worms. Our findings uncover a network of chromatin regulators that control the trans-generational flow of epigenetic information, and suggest that the balance between euchromatic H3K4 and heterochromatic H3K9 methylation regulates trans-generational effects on fertility.

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Section: Discussionmentioning

confidence: 99%

A Histone Methylation Network Regulates Transgenerational Epigenetic Memory in C. elegans

et al. 2014

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“…This result implies that although RSD-2, RSD-6, and SPR-5 repress spermatogenesis gene expression, SPR-5 regulates a distinct repertoire of targets. Thus, the transgenerational sterility phenotype of rsd-2/-6 mutants is distinct from those of alg-3/-4, csr-1, and spr-5 mutants (29).…”

Section: Small Rnas Targeting Spermatogenesis Genes Are Perturbed In Rsdmentioning

confidence: 91%

Caenorhabditis elegans RSD-2 and RSD-6 promote germ cell immortality by maintaining small interfering RNA populations

Sakaguchi

Sarkies

Simon

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Germ cells are maintained in a pristine non-aging state as they proliferate over generations. Here, we show that a novel function of the Caenorhabditis elegans RNA interference proteins RNAi spreading defective (RSD)-2 and RSD-6 is to promote germ cell immortality at high temperature. rsd mutants cultured at high temperatures became progressively sterile and displayed loss of small interfering RNAs (siRNAs) that target spermatogenesis genes, simple repeats, and transposons. Desilencing of spermatogenesis genes occurred in late-generation rsd mutants, although defective spermatogenesis was insufficient to explain the majority of sterility. Increased expression of repetitive loci occurred in both germ and somatic cells of lategeneration rsd mutant adults, suggesting that desilencing of many heterochromatic segments of the genome contributes to sterility. Nuclear RNAi defective (NRDE)-2 promotes nuclear silencing in response to exogenous double-stranded RNA, and our data imply that RSD-2, RSD-6, and NRDE-2 function in a common transgenerational nuclear silencing pathway that responds to endogenous siRNAs. We propose that RSD-2 and RSD-6 promote germ cell immortality at stressful temperatures by maintaining transgenerational epigenetic inheritance of endogenous siRNA populations that promote genome silencing.germ line | fertility | tudor domain protein

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“…H3K4me3 level has been correlated to gene expression (Ruthenburg et al, 2007) and, accordingly, loss or downregulation of KDM5 members has been associated with aberrant transcription, albeit the effect is often limited to minor gene expression changes (Albert et al, 2013;Alvares et al, 2014;Christensen et al, 2007;Dey et al, 2008;Iwase et al, 2007Iwase et al, , 2016Schmitz et al, 2011;Tahiliani et al, 2007). As the contribution of RBR-2 to transcriptional control at a global level has not been assessed, we analyzed the transcriptome of rbr-2(tm3141) worms by RNA sequencing (RNA-seq).…”

Section: Loss Of Rbr-2 Is Associated With Aberrant Gene Expressionmentioning

confidence: 99%

“…Interestingly, animals mutant for rbr-2 are viable and show mild phenotypes related to lifespan regulation (Alvares et al, 2014;Greer et al, 2010Greer et al, , 2011, germline maintenance (Alvares et al, 2014), axon guidance (Mariani et al, 2016) and vulva formation (Christensen et al, 2007). Therefore, C. elegans offers a unique opportunity to study the functional roles of H3K4me3/2 demethylase in the absence of gene redundancy.…”

Section: Introductionmentioning

confidence: 99%

Impaired removal of H3K4 methylation affects cell fate determination and gene transcription

et al. 2016

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Methylation of histone 3 lysine 4 (H3K4) is largely associated with promoters and enhancers of actively transcribed genes and is finely regulated during development by the action of histone methyltransferases and demethylases. H3K4me3 demethylases of the KDM5 family have been previously implicated in development, but how the regulation of H3K4me3 level controls developmental processes is not fully established. Here, we show that the H3K4 demethylase RBR-2, the unique member of the KDM5 family in C. elegans, acts cell-autonomously and in a catalytic-dependent manner to control vulva precursor cells fate acquisition, by promoting the LIN-12/Notch pathway. Using genome-wide approaches, we show that RBR-2 reduces the H3K4me3 level at transcription start sites (TSSs) and in regions upstream of the TSSs, and acts both as a transcription repressor and activator. Analysis of the lin-11 genetic locus, a direct RBR-2 target gene required for vulva precursor cell fate acquisition, shows that RBR-2 controls the epigenetic signature of the lin-11 vulva-specific enhancer and lin-11 expression, providing in vivo evidence that RBR-2 can positively regulate transcription and cell fate acquisition by controlling enhancer activity.

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H3K4 demethylase activities repress proliferative and postmitotic aging

Cited by 46 publications

References 49 publications

A Histone Methylation Network Regulates Transgenerational Epigenetic Memory in C. elegans

A Histone Methylation Network Regulates Transgenerational Epigenetic Memory in C. elegans

Caenorhabditis elegans RSD-2 and RSD-6 promote germ cell immortality by maintaining small interfering RNA populations

Impaired removal of H3K4 methylation affects cell fate determination and gene transcription

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