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PROVIDER: PRJNA392182 | ENA |
REPOSITORIES: ENA
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Project description:SET-9 and SET-26, the C. elegans homologs of human MLL5, are critical for germline development and longevity
| PRJNA392315 | ENA
Project description:SET-9 and SET-26 are highly homologous paralogs that share redundant function in germline development, but SET-26 alone plays a key role in longevity and heat stress response. SET-26 is broadly expressed, but SET-9 is only detectable in the germline, which likely account for their different biological roles. SET-9 and SET-26 bind to H3K4me3 in vitro and in vivo, and their loss results in broadening of H3K4me3 domains. SET-9 and SET-26 also regulate the RNA expression of a subset of their target genes, irrespective of their H3K4me3 status. We propose that SET-9 and SET-26 function to organize local chromatin environment and to regulate the expression of specific target genes, and these activities together contribute to their critical roles in germline development, stress response, and longevity. SET-9 and SET-26 are highly homologous to human MLL5, a factor implicated in leukemia and glioblastoma, and our findings help to provide new insights into MLL5.
2018-05-31 | GSE108848 | GEO
Project description:SET-9 and SET-26 are highly homologous paralogs that share redundant function in germline development, but SET-26 alone plays a key role in longevity and heat stress response. SET-26 is broadly expressed, but SET-9 is only detectable in the germline, which likely account for their different biological roles. SET-9 and SET-26 bind to H3K4me3 in vitro and in vivo, and their loss results in broadening of H3K4me3 domains. SET-9 and SET-26 also regulate the RNA expression of a subset of their target genes, irrespective of their H3K4me3 status. We propose that SET-9 and SET-26 function to organize local chromatin environment and to regulate the expression of specific target genes, and these activities together contribute to their critical roles in germline development, stress response, and longevity. SET-9 and SET-26 are highly homologous to human MLL5, a factor implicated in leukemia and glioblastoma, and our findings help to provide new insights into MLL5.
2018-05-31 | GSE100623 | GEO
Project description:SET-9 and SET-26 are H3K4me3 readers and play critical roles in germline development and longevity
| PRJNA428937 | ENA
Project description:SET-26, HCF-1, and HDA-1 are highly conserved chromatin factors with key roles in development and aging. Here we present mechanistic insights into how these factors regulate gene expression and modulate longevity in C. elegans. We show that SET-26 and HCF-1 cooperate to regulate a common set of genes, and both antagonize the histone deacetylase HDA-1 to limit longevity. We propose a model in which SET-26 recruits HCF-1 to chromatin in somatic cells, where they stabilize each other at the promoters of a subset of genes, particularly mitochondrial function genes, and regulate their expression. HDA-1 opposes SET-26 and HCF-1 on the regulation of a subset of their common target genes and in longevity. Our findings suggest that SET-26, HCF-1, and HDA-1 comprise a mechanism to fine-tune gene expression and longevity and likely have important implications for the mechanistic understanding of how these factors function in diverse organisms, particularly in aging biology.
2024-01-29 | GSE224075 | GEO
Project description:SET-26, HCF-1, and HDA-1 are highly conserved chromatin factors with key roles in development and aging. Here we present mechanistic insights into how these factors regulate gene expression and modulate longevity in C. elegans. We show that SET-26 and HCF-1 cooperate to regulate a common set of genes, and both antagonize the histone deacetylase HDA-1 to limit longevity. We propose a model in which SET-26 recruits HCF-1 to chromatin in somatic cells, where they stabilize each other at the promoters of a subset of genes, particularly mitochondrial function genes, and regulate their expression. HDA-1 opposes SET-26 and HCF-1 on the regulation of a subset of their common target genes and in longevity. Our findings suggest that SET-26, HCF-1, and HDA-1 comprise a mechanism to fine-tune gene expression and longevity and likely have important implications for the mechanistic understanding of how these factors function in diverse organisms, particularly in aging biology.
2024-01-29 | GSE224076 | GEO
Project description: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 a genetic network of chromatin-modifying factors, including the H3K4me1/me2 methyltransferases SET-17 and SET-30, the H3K9me1/me2 methyltransferase MET-2, an H3K9me3 methyltransferase, SET-26, the H3K9me3 demethylase JMJD-2, and an H3K9me reader EAP-1, which regulate the trans-generational flow of epigenetic information. Importantly, genetic ablation of set-17, set-30, jmjd-2, or eap-1 suppresses the progressive transgenerational phenotypes, while loss of SET-26 or MET-2 accelerates the infertility of spr-5 mutant worms. We further show that loss of spr-5 also causes a trans-generational increase in lifespan, which is dependent on these chromatin regulators as well as DAF-36 and DAF-12, which control a germline to soma longevity signaling pathway. These findings suggest that the balance between the euchromatic H3K4 and the heterochromatic H3K9 methylation regulates trans-generational effects on longevity and fertility.
2014-04-08 | GSE52102 | GEO
Project description:The plasticity of ageing suggests that longevity may be controlled epigenetically by specific alterations in chromatin state. The link between chromatin and ageing has mostly focused on histone deacetylation by the Sir2 family1, 2, but less is known about the role of other histone modifications in longevity. Histone methylation has a crucial role in development and in maintaining stem cell pluripotency in mammals3. Regulators of histone methylation have been associated with ageing in worms4, 5, 6, 7 and flies8, but characterization of their role and mechanism of action has been limited. Here we identify the ASH-2 trithorax complex9, which trimethylates histone H3 at lysine 4 (H3K4), as a regulator of lifespan in Caenorhabditis elegans in a directed RNA interference (RNAi) screen in fertile worms. Deficiencies in members of the ASH-2 complex—ASH-2 itself, WDR-5 and the H3K4 methyltransferase SET-2—extend worm lifespan. Conversely, the H3K4 demethylase RBR-2 is required for normal lifespan, consistent with the idea that an excess of H3K4 trimethylation—a mark associated with active chromatin—is detrimental for longevity. Lifespan extension induced by ASH-2 complex deficiency requires the presence of an intact adult germline and the continuous production of mature eggs. ASH-2 and RBR-2 act in the germline, at least in part, to regulate lifespan and to control a set of genes involved in lifespan determination. These results indicate that the longevity of the soma is regulated by an H3K4 methyltransferase/demethylase complex acting in the C. elegans germline. There are 23 samples in total. ASH-2 knock-down increases lifespan in a germline dependent manner. We examined ASH-2 regulated genes that are dependent on the presence of an intact germline using WT or glp-1(e2141ts) mutant worms which develop only 5-15 meiotic germ cells treated with either empty vector (EV) or ash-2 RNAi. We examined gene expression at the L3 stage (when we observe changes in H3K4me3) and at a mid life stage (day 8). The majority of ASH-2 controlled genes were regulated in a germline dependent manner. Samples were collected in triplicate for each condition (but Day 8 N2 (WT) E.V. #3 was excluded from all analysis due to quality issues).
2011-07-08 | E-GEOD-30505 | biostudies-arrayexpress
Project description:How lifespan and the rate of aging are set is a key problem in biology. Small RNAs are conserved molecules that impact diverse biological processes through the control of gene expression. However, in contrast to miRNAs, the role of endo-siRNAs in aging remains unexplored. Here, by combining deep sequencing and genomic and genetic approaches in C.CaenorhabditisC. elegans elegans, we reveal an unprecedented role for endo-siRNA molecules in the maintenance of proteostasis and lifespan extension in germline-less animals. Furthermore, we identify an endo-siRNA-regulated tyrosine phosphatase, which limits the longevity of germline-less animals by restricting the activity of the heat shock transcription factor HSF-1. Altogether, our findings point to endo-siRNAs as a link between germline removal and the HSF-1 proteostasis and longevity-promoting somatic pathway. This establishes a role for endo siRNAs in the aging process and identifies downstream genes and physiological processes that are regulated by the endo siRNAs to affect longevity.
2020-04-03 | GSE128935 | GEO
Project description: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 a genetic network of chromatin-modifying factors, including the H3K4me1/me2 methyltransferases SET-17 and SET-30, the H3K9me1/me2 methyltransferase MET-2, an H3K9me3 methyltransferase, SET-26, the H3K9me3 demethylase JMJD-2, and an H3K9me reader EAP-1, which regulate the trans-generational flow of epigenetic information. Importantly, genetic ablation of set-17, set-30, jmjd-2, or eap-1 suppresses the progressive transgenerational phenotypes, while loss of SET-26 or MET-2 accelerates the infertility of spr-5 mutant worms. We further show that loss of spr-5 also causes a trans-generational increase in lifespan, which is dependent on these chromatin regulators as well as DAF-36 and DAF-12, which control a germline to soma longevity signaling pathway. These findings suggest that the balance between the euchromatic H3K4 and the heterochromatic H3K9 methylation regulates trans-generational effects on longevity and fertility. EAP-1 binding ChIPseq libraries were prepared from 50 ul of packed young adult worms which were maintained at 16 degrees until the appropriate generation and then shifted to 25 degrees after birth. Two biological repeats were generated for wildtype and generation 20 spr-5(by101) mutant worms and a single repeat for generation 10. There were four input samples and eap-1 null mutant worms were also analyzed.
2014-04-08 | E-GEOD-52102 | biostudies-arrayexpress