Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transgenerational inheritance of altered H3K27me3 in wildtype Caenorhabditis elegans

ABSTRACT: Epigenetic inheritance provides mutation-free mechanisms for phenotypic adaptation, including modifications to DNA or DNA-associated proteins that create patterns of heritable gene regulation. However, the limits and regulation of this inheritance remain incompletely understood. Here, we developed a C. elegans system to study the transgenerational epigenetic inheritance of H3K27me3, a conserved histone posttranslational modification associated with gene repression. We find that induced alterations of the genome-wide H3K27me3 landscape and the associated fertility defects persist for many generations in genetically wildtype descendants under selective pressure. We uncover that the inheritance of the altered H3K27me3 landscape involves an initiation phase that relies on SET-32/H3K23me3 and a maintenance phase that requires MES-4/H3K36me3. Our results demonstrate that epigenetic inheritance can act as a mutation-independent, heritable mechanism of adaptation.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE337109 | GEO | 2026/08/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The chromatin modifiers SET-25 and SET-32 are required for initiation but not long-term maintenance of transgenerational epigenetic inheritance

Project description:Some epigenetic modifications are inherited from one generation to the next, providing a potential mechanism for the inheritance of environmentally acquired traits. Transgenerational inheritance of RNA interference phenotypes in C. elegans provides an excellent model to study this phenomenon, and whilst studies have implicated both chromatin modifications and small RNA pathways in heritable silencing their relative contributions remain unclear. Here we demonstrate that the histone methyltransferases SET-25 and SET-32 are required for the establishment of a transgenerational silencing signal, but not for long-term maintenance of this signal between subsequent generations suggesting that transgenerational epigenetic inheritance is a multi-step process, with distinct genetic requirements for establishment and maintenance of heritable silencing. Furthermore, small RNA sequencing reveals that the abundance of secondary siRNA (thought to be the effector molecules of heritable silencing) does not correlate with silencing phenotypes. Together, our results suggest that the current mechanistic models of epigenetic inheritance are incomplete.

2018-10-30 | PXD008754 | Pride

Heritable human Polycomb silencing is locus-dependent and requires H2AK119ub1 self-propagation

Project description:Heritable gene silencing is essential for the development of multicellular organisms. Polycomb repressive complexes 1 and 2 (PRC1 and 2) catalyze and recognize histone H2A lysine 119 mono-ubiquitination (H2AK119ub1) and histone H3 lysine 27 trimethylation (H3K27me3), respectively, to mediate heritable gene silencing, but the mechanism of inheritance is not fully understood. Using an inducible gene silencing strategy, we show that the epigenetic inheritance of Polycomb silencing in human cells is strongly dependent on local DNA sequences and chromatin environment. In addition, we find that inheritance is not strictly dependent on H3K27me3 recognition and can be partially achieved by H2AK119ub1 catalysis and recognition, independently of H3K27me3. These findings demonstrate that locus specific features and H2AK119ub1 play key roles in inheritance of Polycomb silencing in human cells.

2024-05-15 | GSE209986 | GEO

Two H3K23 histone methyltransferases, SET-32 and SET-21, function synergistically to promote nuclear RNAi-mediated transgenerational epigenetic inheritance in Caenorhabditis elegans

Project description:Nuclear RNAi in C. elegans induces a set of transgenerationally heritable marks of H3K9me3, H3K23me3, and H3K27me3 at the target genes. The function of H3K23me3 in the nuclear RNAi pathway is largely unknown due to the limited knowledge of H3K23 histone methyltransferase (HMT). In this study we identified SET-21 as a novel H3K23 HMT. By taking combined genetic, biochemical, and genomic approaches we found that SET-21 functions synergistically with a previously reported H3K23 HMT SET-32 to deposit H3K23me3 at the native targets of germline nuclear RNAi. We identified a subset of nuclear RNAi targets that became transcriptionally activated in the set-21;set-32 double mutant. SET-21 and SET-32 are also required for a robust transgenerational gene silencing induced by exogenous dsRNA. The set-21;set-32 double mutant exhibited an enhanced mortal germline phenotype at a high temperature compared to the set-32 single mutant. Together, these results support a model in which H3K23 HMTs SET-21 and SET-32 function cooperatively to ensure the robustness of germline nuclear RNAi and promotes the germline immortality under the heat stress.

2024-12-06 | PXD052034 | Pride

C. elegans nuclear RNAi factor SET-32 is an H3K23 methyltransferase and deposits the transgenerational heritable modification of H3K23me3

Project description:Nuclear RNAi provides a highly tractable system to study RNA-mediated chromatin changes and epigenetic inheritance. Recent studies indicate that nuclear RNAi-mediated heterochromatin is highly complex in its regulation and function. The knowledge of histone modifications that are involved in nuclear RNAi and the corresponding histone modifying enzymes remains limited. In this study, we show that the heterochromatin mark H3K23me3 is induced by nuclear RNAi at both exogenous and endogenous targets in C. elegans. In addition, RNAi-induced H3K23me3 can be inherited for at least four generations. We also demonstrate that the histone methyltransferase SET-32, methylates H3K23 in vitro. Both set-32 and the germline nuclear RNAi Argonaute, hrde-1, are required for nuclear RNAi-induced H3K23me3 in vivo. Our data poise H3K23me3 as a chromatin modification involved in the nuclear RNAi pathway and provides the field with a new target for uncovering the role of heterochromatin in transgenerational epigenetic silencing.

2020-05-01 | GSE141347 | GEO

Quantification of histone H3 and H4 modifications by mass spectrometry in wildtype and MCM2-2A mutants of mice ESCs

Project description:During DNA replication modified parental histones H3-H4 are segregated almost symmetrically to the two daughter DNA strands enabling mitotic inheritance of histone PTMs. Whether heritable histone modifications confer epigenetic regulation by maintaining chromatin states and gene expression is unclear. Using MCM2 histone-binding mutant embryonic stem cells (ESCs) and mass spectrometry, we show that asymmetric segregation of parental histones to the leading strand causes imbalanced inheritance of histone H3K27 methylations to daughter cells.

2023-08-30 | PXD020326 | Pride

Transgenerational inheritance of mitochondrial stress adaptation in C. elegans

Project description:Using Caenorhabditis elegans to investigate environmental cues-induced mitochondrial dysfunction, we found that exposure to electron transport chain (ETC) inhibitors at the parental generation initiates the transmission of heritable information to descendants and make descendants stress-adaptive. This mitochondrial stress adaptation phenotype can persist for at least three generations. Animals lacking histone H3K4me3 chromatin modifiers, or the methyltransferase of N6-methyldeoxyadenosine (6mA), lose the ability to initiate stress adaptation in progeny. H3K4me3 plays a role upstream of 6mA, while both mark promoter regions of mitochondrial unfolded protein response (UPR mt ) genes and activate the UPR mt pathway to alleviate mitochondrial damage.

2017-07-26 | GSE85835 | GEO

A Composite DNA Element that Functions as a Maintainer Required for Epigenetic Inheritance of Heterochromatin

Project description:Epigenetic inheritance of heterochromatin requires DNA sequence-independent propagation mechanisms, coupling to RNAi, or input from DNA sequence, but how DNA contributes to inheritance is not understood. Here, we identify a DNA element (termed “maintainer”) that is sufficient for epigenetic inheritance of preexisting histone H3 lysine 9 methylation (H3K9me) and heterochromatin in Schizosaccharomyces pombe, but cannot establish de novo gene silencing in wild-type cells. This maintainer is a composite DNA element with binding sites for the Atf1/Pcr1 and Deb1 transcription factors and the Origin Recognition Complex (ORC), located within a 130-base pair region, and can be converted to a silencer in cells with lower rates of H3K9me turnover, suggesting that it participates in recruiting the H3K9 methyltransferase Clr4/Suv39h. These results suggest that, in the absence of RNAi, histone H3K9me is only heritable when it can collaborate with maintainer-associated DNA-binding proteins that help recruit the enzyme responsible for its epigenetic deposition.

2022-10-14 | PXD027214 | Pride

Two H3K23 histone methyltransferases, SET-32 and SET-21, function synergistically to promote germline nuclear RNAi, proper endogenous siRNA expression, and germline immortality in Caenorhabditis elegans [ChIP-seq]

Project description:Nuclear RNAi in C. elegans induces a set of transgenerationally heritable marks of H3K9me3, H3K23me3, and H3K27me3 at the target genes. The function of H3K23me3 in the nuclear RNAi pathway is largely unknown due to the limited knowledge of H3K23 histone methyltransferase (HMT). In this study we identified SET-21 as a novel H3K23 HMT. By taking combined genetic, biochemical, and genomic approaches we found that SET-21 functions synergistically with a previously reported H3K23 HMT SET-32 to deposit H3K23me3 at the native targets of germline nuclear RNAi. We identified a subset of nuclear RNAi targets become transcriptionally activated in the set-21;set-32 double mutant. SET-21 and SET-32 are also required for a robust transgenerational gene silencing induced by exogenous dsRNA. The loss of SET-21 and SET-32 leads to a mortal germline phenotype, similar to mutations of the core nuclear RNAi component. Together, these results support a model in which H3K23 HMTs SET-21 and SET-32 ensure the robustness of germline nuclear RNAi and promotes the germline immortality at a high temperature.

2024-11-01 | GSE266184 | GEO

Project description:Nuclear RNAi in C. elegans induces a set of transgenerationally heritable marks of H3K9me3, H3K23me3, and H3K27me3 at the target genes. The function of H3K23me3 in the nuclear RNAi pathway is largely unknown due to the limited knowledge of H3K23 histone methyltransferase (HMT). In this study we identified SET-21 as a novel H3K23 HMT. By taking combined genetic, biochemical, and genomic approaches we found that SET-21 functions synergistically with a previously reported H3K23 HMT SET-32 to deposit H3K23me3 at the native targets of germline nuclear RNAi. We identified a subset of nuclear RNAi targets become transcriptionally activated in the set-21;set-32 double mutant. SET-21 and SET-32 are also required for a robust transgenerational gene silencing induced by exogenous dsRNA. The loss of SET-21 and SET-32 leads to a mortal germline phenotype, similar to mutations of the core nuclear RNAi component. Together, these results support a model in which H3K23 HMTs SET-21 and SET-32 ensure the robustness of germline nuclear RNAi and promotes the germline immortality at a high temperature.

2024-11-01 | GSE266183 | GEO

Project description:Nuclear RNAi in C. elegans induces a set of transgenerationally heritable marks of H3K9me3, H3K23me3, and H3K27me3 at the target genes. The function of H3K23me3 in the nuclear RNAi pathway is largely unknown due to the limited knowledge of H3K23 histone methyltransferase (HMT). In this study we identified SET-21 as a novel H3K23 HMT. By taking combined genetic, biochemical, and genomic approaches we found that SET-21 functions synergistically with a previously reported H3K23 HMT SET-32 to deposit H3K23me3 at the native targets of germline nuclear RNAi. We identified a subset of nuclear RNAi targets become transcriptionally activated in the set-21;set-32 double mutant. SET-21 and SET-32 are also required for a robust transgenerational gene silencing induced by exogenous dsRNA. The loss of SET-21 and SET-32 leads to a mortal germline phenotype, similar to mutations of the core nuclear RNAi component. Together, these results support a model in which H3K23 HMTs SET-21 and SET-32 ensure the robustness of germline nuclear RNAi and promotes the germline immortality at a high temperature.

2024-11-01 | GSE266182 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data