Biology subjects

Guang, S.

Publications and source records attributed to Guang, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Identification of a somatic H3K23me3 methyltransferase SET-19 in C. elegans

Histone methylation plays essential roles in modulating chromatin organization and gene expression. H3K23 methylation is a conserved histone modification, yet its biological roles and the enzymes responsible for its deposition remain poorly understood. Here, we show that the loss of set-19 leads to a pronounced reduction in H3K23 methylation in C. elegans, as revealed by quantitative mass spectrometry, western blotting, and immunofluorescence staining. In vitro biochemical assays show that recombinant SET-19 proteins purified from E. coli directly catalyze H3K23 methylation. Genome-wide chromatin immunoprecipitation assays reveal that H3K23me3 is enriched at heterochromatic regions and that loss of set-19 alters H3K23me3 levels, accompanied by derepression of gene expression. Genetic analyses indicate that SET-19 is dispensable for both germline and somatic RNAi as well as transgenerational epigenetic inheritance of RNAi. SET-19 is predominantly expressed in somatic cells and specifically mediates H3K23me3 deposition in somatic tissues. The loss of set-19 causes a developmental delay without affecting fertility. Together, our results identify SET-19 as a somatic H3K23 methyltransferase and link H3K23me3 to gene repression in C. elegans.

genetics↗

bioRxiv2026

Heat stress-induced condensation of G3BP1 in perinuclear P-bodies in C. elegans' germline

Stress granules (SGs) are essential subcellular assemblies that enable cells to adapt to environmental stress, and their dynamic assembly and disassembly are critical for maintaining cellular homeostasis and reproductive capacity. However, the function and regulation of stress granules in germline cells remain mysterious. In this study, we characterized the function of GTBP-1, the homolog of human G3BP1, in response to heat stress in Caenorhabditis elegans and elucidated its regulation in stress granule dynamics. gtbp-1 mutants exhibit pronounced temperature-dependent biodirectional reproductive characteristics. At lower temperatures, their brood size is higher than that of wild-type animals, whereas at 25 {degrees}C they are completely sterile. GTBP-1 is diffusely distributed at normal culturing temperatures but forms perinuclear stress granules upon heat shock in the germline. While the NTF2 domain is essential for germline stress granule formation, other domains, including the IDR, RRM and RGG, are required for the recovery phase after heat shock. GTBP-1 stress granules colocalize with the P-bodies, but not with other germ granules. The depletion of P-bodies prohibited the perinuclear GTBP-1 stress granule formation. A combination of forward genetic screening together with RNAi-based candidate screening identified the P body components, the RNA helicase LAF-1, the SUMO protein SMO-1, and the mTOR pathway effector RSKS-1(S6K) as key regulators of GTBP-1 germline stress granule formation. Together, this work revealed that germline stress granules may be subjected to multiple layers of regulations and GTBP-1 may safeguards reproductive homeostasis under temperature stress by coordinating germline stress granule condensation. Author SummaryReproduction is particularly vulnerable to environmental stress, yet germ cells must remain functional to ensure fertility. How germ cells protect themselves under stressful conditions is still not well understood. In this study, we used the nematode Caenorhabditis elegans to examine how germ cells respond to heat stress, focusing on GTBP-1, a conserved protein involved in stress granule formation. We found that GTBP-1 plays contrasting roles depending on temperature: under normal conditions it restrains reproduction, whereas under heat stress it becomes essential for maintaining fertility. When animals are exposed to elevated temperature, GTBP-1 rapidly forms granules around the nuclei of germ cells, these granules assemble at sites occupied by processing bodies, another type of RNA-containing structure, revealing a close spatial relationship between two stress-responsive compartments. We also found that this process is regulated by conserved factors involved in RNA regulation and nutrient-responsive signaling. Together, our findings show how germ cells reorganize RNA-protein assemblies to preserve reproductive capacity under stressful conditions.

genetics↗

bioRxiv2025

rRNA intermediates dictate nucleolar architecture in C. elegans

The nucleolus is a multilayered, membraneless organelle essential for rRNA transcription, processing and ribosome assembly; however, it remains largely unclear whether and how these molecular events coordinate the organization of the multilayered nucleolar structure. We previously reported that the accumulation of 27SA2 rRNA upon the loss of a particular subset of RPL proteins elicits nucleolar reshaping, resulting in the formation of nucleolar rings and vacuoles in C. elegans. Here, we systematically investigated the effects of pre-18S rRNA processing and rRNA transcription on nucleolar structure and reported that defects in these molecular events result in reorganization of the nucleolar architecture. In particular, the depletion of a special subset of small ribosomal subunit proteins (RPSs), namely, class I RPSs, induces a concentric three-layered nucleolar architecture; the inhibition of rRNA transcription induces another three-layered architecture, a sandwich-like nucleoli. Via fluorescence imaging, we found that nucleolar proteins undergo demixing and spatial redistribution into distinct subnucleolar regions during nucleolar structure reorganization. Tracking the subcellular localization of rDNA via a lacI::tagRFP/lacO system revealed that rDNA also redistributed upon nucleolar reorganization. We further identified the Ce.22S rRNA intermediate, which accumulates upon the loss of class I RPSs and regulates the reorganization of the nucleolar structure. Moreover, the conserved nucleolar protein NUCL-1/nucleolin is essential for nucleolar architecture reorganization and regulates the development of nematodes during impaired rRNA production. Together, these findings reveal that the nucleolar structure is orchestrated by the status of rRNA biogenesis and that the accumulation of particular rRNA intermediates can direct the organization of specific nucleolar architectures and the spatial mixing/demixing behavior of the nucleolar proteome.

genetics↗

bioRxiv2025

The H3K27me3 reader UAD-2 recruits a TAF-12-containing transcription condensates to initiate piRNA expression within heterochromatic clusters

Metazoans utilize the small RNA pathway to regulate gene expression and maintain genome integrity. This pathway directs histone H3 lysine 9 tri-methylation (H3K9me3) or histone H3 lysine 27 tri-methylation (H3K27me3) at target loci to induce transcriptional gene silencing. Interestingly, some small RNAs are generated from genomic loci enriched in H3K9me3 or H3K27me3. However, the transcription mechanism of small RNA precursors from these heterochromatic regions remains unclear. In C. elegans, piRNAs originate from two genomic clusters enriched with H3K27me3 marks, which recruit the H3K27me3 reader UAD-2 and the upstream sequence transcription complex (USTC). Here, we demonstrate that piRNA transcription in C. elegans relies on TAF-12, a subunit of the basal transcription factor IID (TFIID). Depletion of TAF-12 reduces the production of both piRNA precursors and mature piRNAs. TAF-12 interacts with UAD-2 and facilitates piRNA focus formation in germ cell nuclei. We further show that TAF-12 triggers piRNA transcription by recruiting the RNA polymerase II subunit RPB-5, the Mediator complex subunit MDT-8, and the general transcription factors GTF-2F2 and GTF-2H2C. Thus, piRNA transcription within heterochromatic regions depends on the collaboration between histone modification readers, piRNA-specific transcription factors, and core transcription machinery.

genetics↗

bioRxiv2025

A SET domain-containing protein and HCF-1 maintain transgenerational epigenetic memory

Epigenetic information can be inherited through a process known as transgenerational epigenetic inheritance (TEI). TEI can be initiated and maintained by small RNAs and histone modifications. The latter includes histone methylation, deposited by proteins with methyltransferase activity, including SET domain-containing proteins. Other SET domain-containing proteins with no catalytic methyltransferase activity also adopt roles in chromatin and gene expression regulation. Here, we describe SET-24, a SET domain-containing protein in Caenorhabditis elegans that belongs to a family of catalytically inactive SET proteins. SET-24 localises to germline nuclei and is required for germline immortality. Additionally, the inheritance of small RNA-driven epigenetic silencing is compromised in set-24 mutants. Using quantitative proteomics and yeast two-hybrid assays, we found that SET-24 interacts with Host Cell Factor 1 (HCF-1), a protein involved in epigenetic regulation and associated with known chromatin remodelling complexes, like COMPASS, which deposits H3K4me3. In set-24 mutants, hundreds of genes display increased H3K4me3 levels at their transcription start sites. While these changes are not matched at the transcriptional level, small RNA production is disrupted in approximately one fifth of those genes, which are normally targeted by small RNA pathways. We propose that SET-24 is a factor required to maintain epigenetic memory in the germline by maintaining a chromatin environment permissible to small RNA biogenesis over generations.

molecular biology↗

bioRxiv2025

Red Light-Activated Reversible Inhibition of Protein Functions by Assembled Trap

Red light offers strong tissue penetration and low phototoxicity, making it an attractive option for optogenetic applications. However, the available red light-inducible optogenetic tools are rather limited. Here, we present a novel red light-induced protein clustering system, namely R-LARIAT (Red Light-Activated Reversible Inhibition by Assembled Trap), that controls protein functions in a spatiotemporal manner. Our system capitalizes on the rapid and reversible binding of LDBs (nanobodies-based dimerization binders) to a bacterial phytochrome DrBphP, which uses a mammalian endogenous biliverdin chromophore to absorb red light. An anti-GFP nanobody fused with LDBs allows this method to quickly trap a wide variety of GFP-tagged proteins into light-induced protein clusters. Strikingly, our system exhibits an excellent performance in clustering efficiency with high light sensitivity and stability, it can function even when shielded by multiple glass plates. By utilizing the R-LARIAT system to trap and sequester tubulin, cell cycle progression can be blocked in HeLa cells. Therefore, the R-LARIAT system takes advantage of red light with greater tissue penetration and holds the potential to precisely control protein functions in living organisms.

cell biology↗

bioRxiv2024

TurboID-based proximity labeling identifies novel germline proteins that maintain E granule integrity and small RNA homeostasis in C. elegans

Germ granules are biomolecular condensates composed of RNA and proteins that play crucial roles in RNA metabolism and posttranscriptional gene regulation. C. elegans germ granules consist of at least seven distinct subcompartments, including P granules, Z granules, Mutator foci, SIMR foci, P-bodies, D granules and E granules. Among these condensates, the E granule, which is nonrandomly positioned within the germ granule, is required for the production of a specialized class of small interfering RNAs (siRNAs). However, the mechanisms underlying E granule formation and its functional significance remain largely unexplored. In this study, via the use of TurboID- based proximity labeling technology combined with an RNAi-based reverse genetic screen, we identified two novel components of the E granule, EGC-2/C27B7.5 and EGC-3/F59G1.8, which initiate E granule assembly. The depletion of EGC-2 or EGC- 3 disrupts the perinuclear localization of the EGO and PICS complexes, both of which are enriched in E granules and are required for E-class siRNA and piRNA biogenesis, respectively. Small RNAomic analyses revealed that both EGC-2 and EGC-3 promote the production of 5 E-class siRNA, whereas prohibiting piRNA maturation. Taken together, our results elucidate the roles of EGC-2 and EGC-3 in maintaining E granule integrity and small RNA homeostasis, and suggest that intracellular condensation may exert distinct regulatory effects on different biological processes. Additionally, the combination of proximity labeling technology and reverse genetic screening provides a robust strategy for studying the assembly of biomolecular condensates.

genetics↗

bioRxiv2024

Peri-centrosomal localization of small interfering RNAs in C. elegans

The centrosome is the microtubule-organizing center and a crucial part of cell division. Centrosomal RNAs (cnRNAs) have been reported to enable precise spatiotemporal control of gene expression during cell division in many species. Whether and how cnRNAs exist in C. elegans are unclear. Here, using the nuclear RNAi Argonaute protein NRDE-3 as a reporter, we observed potential peri-centrosome localized small interfering (si)RNAs in C. elegans. NRDE-3 was previously shown to associate with pre-mRNAs and pre-rRNAs via a process involving the presence of complementary siRNAs. We generated a GFP-NRDE-3 knock-in transgene through CRISPR/Cas9 technology and observed that NRDE-3 formed peri-centrosomal foci neighboring the tubulin protein TBB-2, other centriole proteins and pericentriolar material (PCM) components in C. elegans embryos. The peri-centrosomal accumulation of NRDE-3 depends on RNA-dependent RNA polymerase (RdRP)-synthesized 22G siRNAs and the PAZ domain of NRDE-3, which is essential for siRNA binding. Mutation of eri-1, ergo-1, or drh-3 significantly increased the percentage of pericentrosome-enriched NRDE-3. At the metaphase of the cell cycle, NRDE-3 was enriched in both the peri-centrosomal region and the spindle. Moreover, the integrity of centriole proteins and pericentriolar material (PCM) components is also required for the peri-centrosomal accumulation of NRDE-3. Therefore, we concluded that siRNAs could accumulate in the peri-centrosomal region in C. elegans and suggested that the peri-centrosomal region may also be a platform for RNAi-mediated gene regulation.

genetics↗

bioRxiv2024

ER-GUARD: an evolutionarily conserved antioxidant defense system at ER membranes

Oxidative protein folding in the endoplasmic reticulum (ER) is essential for all eukaryotic cells yet generates hydrogen peroxide (H2O2), a reactive oxygen species (ROS). The ER-transmembrane protein that provides reducing equivalents to ER and guards the cytosol for antioxidant defense remains unidentified. Here we combine AlphaFold2-based and functional reporter screens in C. elegans to discover a previously uncharacterized and evolutionarily conserved protein ERGU-1 that fulfills these roles. Deleting C. elegans ERGU-1 causes excessive H2O2 and transcriptional gene up-regulation through SKN-1, homolog of mammalian antioxidant master regulator NRF2. ERGU-1 deficiency also impairs organismal reproduction and behavioral responses to H2O2. Both C. elegans and human ERGU-1 proteins localize to ER membranes and form network reticulum structures. Human and Drosophila homologs of ERGU-1 can rescue C. elegans mutant phenotypes, demonstrating evolutionarily ancient and conserved functions. In addition, purified ERGU-1 and human homolog TMEM161B exhibit redox-modulated oligomeric states. Together, our results reveal an ER-membrane-specific protein machinery for peroxide detoxification and suggest a previously unknown and conserved mechanisms for antioxidant defense in animal cells.

cell biology↗

bioRxiv2024

Compartmentalized localization of perinuclear proteins within germ granules in C. elegans

Biomolecular condensates are nonmembrane-enclosed organelles that play important roles in distinct biological processes. Germ granules are RNA-rich condensates that are often docked on the cytoplasmic surface of germline nuclei and exist in a variety of organisms. The C. elegans germ granule is a condensate that is subcompartmentalized into at least 6 distinct regions, including the P granule, Z granule, E granule, Mutator foci, SIMR foci and P-body. Although a number of perinuclear proteins have been found to be enriched in germ granules, their precise localization within the subcompartments of germ granules is still unclear. Here, we systematically labeled perinuclear localized proteins with fluorescent proteins via CRISPR/Cas9 technology and further explored the perinuclear localization of these proteins. Using this nematode strain library, we identified a series of proteins localized in Z or E granules. We found that proteins that participate in distinct piRNA processing steps were localized in particular subcompartments, including the P-, Z-, and E-granules. We further identified a novel subcompartment, the D granule, which was enriched between the P granule and the nuclear pore complex. Finally, we analyzed the perinuclear localization of these germ granule subcompartments in mip-1/eggd-1 mutants and found that the LOTUS domain protein MIP-1/EDDG-1 was required for the establishment of the multiphase architecture of germ granules. Overall, our work revealed germ granule architecture and redefined the localization of perinuclear proteins within germ granules. Additionally, the library of genetically modified nematode strains expressing peri-nuclear proteins labeled with fluorescent tags will facilitate research on germ granules in C. elegans.

cell biology↗

bioRxiv2024

Nucleolar stress induced the formation of a nucleolar stress body via the NOSR-1/NUMR-1 axis in Caenorhabditis elegans

Environmental stimuli not only alter gene expression profiles but also induce structural changes in cells. How distinct nuclear bodies respond to cellular stress is poorly understood. Here, we identified a new subnuclear organelle named the nucleolar stress body (NoSB), the formation of which was induced by the inhibition of rRNA transcription or inactivation of rRNA processing and maturation in C. elegans. NoSB did not colocalize with other previously described subnuclear organelles. We conducted forward genetic screening and identified a new bZIP transcription factor, named nucleolar stress response-1 (NOSR-1), that is required for NoSB formation. The inhibition of rRNA transcription or inactivation of rRNA processing and maturation increased nosr-1 expression. By using transcriptome analysis of wild-type animals subjected to different nucleolar stress conditions and nosr-1 mutants, we identified that the SR-like protein NUMR-1 (nuclear localized metal responsive) is the target of NOSR-1. Interestingly, NUMR-1 is a component of NoSB and itself per se is required for the formation of NoSB. We concluded that the NOSR-1/NUMR-1 axis likely responds to nucleolar stress and mediates downstream stress-responsive transcription programs and subnuclear morphology alterations in C. elegans.

cell biology↗

bioRxiv2023

Spatially clustered piRNA genes promote the transcription of piRNAs via condensate formation of the H3K27me3 reader UAD-2

PIWI-interacting RNAs (piRNAs) are essential for maintaining genome integrity and fertility in various organisms. In flies and nematodes, piRNA genes are encoded in heterochromatinized genomic clusters. The molecular mechanisms of piRNA transcription remain intriguing. Through unique molecular indexed-small RNA sequencing and chromosome editing, we discovered that spatial aggregation of piRNA genes enhances their transcription in nematodes. The heterochromatinized piRNA genome recruits the piRNA transcription complex USTC (including PRDE-1, SNPC-4, TOFU-4, and TOFU-5) and the H3K27me3 reader UAD-2, which phase separate into droplets to initiate piRNA transcription. We searched for factors that regulate piRNA condensate formation and isolated the SUMO E3 ligase GEI-17 as inhibiting and the SUMO protease TOFU-3 as promoting condensate formation, thereby regulating piRNA production. Our study revealed that spatial aggregation of piRNA genes, phase separation and deSUMOylation may benefit the organization of functional biomolecular condensates to direct piRNA transcription in the heterochromatinized genome.

molecular biology↗

bioRxiv2023

Germ granule compartments coordinate specialized small RNA production

Germ granules are biomolecular condensates present in most animal germ cells. One function of germ granules is to help maintain germ cell totipotency by organizing mRNA regulatory machinery, including small RNA-based gene regulatory pathways. The C. elegans germ granule is compartmentalized into multiple subcompartments whose biological functions are largely unknown. Here, we identify a new subcompartment of the C. elegans germ granule, which we term the E compartment. The E compartment is nonrandomly positioned within the germ granule. We identified five proteins that localize to the E compartment, including the RNA-dependent RNA polymerase (RdRP) EGO-1, the Dicer-related helicase DRH-3, the Tudor domain-containing protein EKL-1, and two intrinsically disordered proteins, EGC-1 and ELLI-1. Localization of EGO-1 to the E granule enables synthesis of a specialized class of 22G RNAs, which derive exclusively from 5 regions of a subset of germline-expressed mRNAs. Defects in E compartment assembly elicit disordered production of endogenous siRNAs, which disturbs fertility and the RNAi response. Our results define a new subcompartment of the C. elegans germ granule and suggest that one function of germ granule compartmentalization is to facilitate the localized production of specialized classes of small regulatory RNAs.

cell biology↗

bioRxiv2023

Acquired stress resilience through bacteria-to-nematode horizontal gene transfer

Natural selection drives acquisition of organismal resilience traits to protect against adverse environments. Horizontal gene transfer (HGT) is an important evolutionary mechanism for the acquisition of novel traits, including metazoan acquisition of functions in immunity, metabolism, and reproduction via interdomain HGT (iHGT) from bacteria. We report that the nematode gene rml-3, which was acquired by iHGT from bacteria, enables exoskeleton resilience and protection against environmental toxins in C. elegans. Phylogenetic analysis reveals that diverse nematode RML-3 proteins form a single monophyletic clade most highly similar to bacterial enzymes that biosynthesize L-rhamnose to build cell wall polysaccharides. C. elegans rml-3 is regulated in developing seam cells by heat stress and stress-resistant dauer stage. Importantly, rml-3 deficiency impairs cuticle integrity, barrier functions and organismal stress resilience, phenotypes that are rescued by exogenous L-rhamnose. We propose that iHGT of an ancient bacterial rml-3 homolog enables L-rhamnose biosynthesis in nematodes that facilitates cuticle integrity and organismal resilience in adaptation to environmental stresses during evolution. These findings highlight the remarkable contribution of iHGT on metazoan evolution that is conferred by the domestication of bacterial genes.

genetics↗

bioRxiv2023

Early-life stress triggers long-lasting organismal resilience and longevity via tetraspanin

Early-life stress experiences can produce lasting impacts on organismal adaptation and fitness. How transient stress elicits memory-like physiological effects is largely unknown. Here we show that early-life thermal stress strongly up-regulates tsp-1, a gene encoding the conserved transmembrane tetraspanin in C. elegans. TSP-1 forms prominent multimers and stable web- like structures critical for membrane barrier functions in adults and during aging. The up- regulation of TSP-1 persists even after transient early-life stress. Such regulation requires CBP- 1, a histone acetyl-transferase that facilitates initial tsp-1 transcription. Tetraspanin webs form regular membrane structures and mediate resilience-promoting effects of early-life thermal stress. Gain-of-function TSP-1 confers marked C. elegans longevity extension and thermal resilience in human cells. Together, our results reveal a cellular mechanism by which early-life thermal stress produces long-lasting memory-like impact on organismal resilience and longevity. TeaserStudies reveal mechanisms of how early-life heat exposure produces long-lasting benefits on longevity in the nematode C. elegans.

physiology↗

bioRxiv2023

rRNA intermediates coordinate the multilayered nucleolar phase transition in C. elegans

The nucleolus is the most prominent membraneless organelle within the nucleus and plays essential roles in rRNA transcription and processing and ribosome assembly. How the structure of the nucleolus is maintained and regulated is poorly understood. Here, we identified two types of nucleoli in C. elegans. Type I nucleoli are spherical, and rRNA transcription and processing factors are evenly distributed throughout the nucleolus. In type II nucleoli, rRNA transcription and processing factors exclusively accumulate in the periphery rim, which is named the nucleolar ring. The hollow vacuole inside the nucleolar ring contains proteins that usually localize in the nucleoplasm but are capable of exchanging contents across the ring. The high-order structure of the nucleolus is dynamically regulated in C. elegans. Faithful rRNA processing is important to maintain the spherical structure of the nucleoli. The depletion of a class of rRNA processing factors, for example, class I ribosomal proteins of the large subunit (RPL), which are involved in 27SA2 rRNA processing, reshaped spherical nucleoli to a ring-shaped nucleolar structure. The inhibition of RNAP I transcription and depletion of two conserved nucleolar factors, nucleolin and fibrillarin, prohibits the formation of the nucleolar ring. We concluded that the integrity of nucleoli is highly dependent on rRNA processing and maturation, which may provide a mechanism to coordinate structure maintenance and gene expression.

cell biology↗

bioRxiv2022

A ZTF-7/RPS-2 complex mediates the cold-warm response in C. elegans

Temperature greatly affects numerous biological processes in all organisms. How multicellular organisms respond to and are impacted by hypothermic stress remains elusive. Here, we found that cold-warm stimuli induced depletion of the RNA exosome complex in the nucleoli but enriched it in the nucleoplasm. To further understand the function and mechanism of cold-warm stimuli, we conducted forward genetic screening and identified ZTF-7, which is required for RNA exosome depletion from nucleoli upon transient cold-warm exposure in C. elegans. ZTF-7 is a putative ortholog of human ZNF277 that may contribute to language impairments. Immunoprecipitation followed by mass spectrometry (IP-MS) found that ZTF-7 interacted with RPS-2, which is a ribosomal protein of the small subunit and participates in pre-rRNA processing. A partial depletion of RPS-2 and other proteins of the small ribosomal subunit blocked the cold-warm stimuli-induced reduction of exosome subunits from the nucleoli. These results established a novel mechanism by which C. elegans responds to environmental cold-warm exposure.

genetics↗

bioRxiv2022

Systematic characterization of chromodomain proteins revealsan H3K9me1/2 reader regulating aging in C. elegans

The chromatin organization modifier domain (chromodomain) is an evolutionally conserved motif across eukaryotic species. The chromodomain mainly functions as a histone methyl-lysine reader to modulate gene expression, chromatin spatial conformation and genome stability. Mutations or aberrant expression of chromodomain proteins can result in cancer and other human diseases. Here, we systematically tagged chromodomain proteins with green fluorescent protein (GFP) using CRISPR/Cas9 technology in C. elegans. By combining ChIP-seq analysis and imaging, we delineated a comprehensive expression and functional map of chromodomain proteins. We then conducted a candidate-based RNAi screening and identified factors that regulate the expression and subcellular localization of the chromodomain proteins. Specifically, we revealed a new H3K9me1/2 reader, CEC-5, both by in vitro biochemistry and in vivo ChIP assays. MET-2, an H3K9me1/2 writer, is required for CEC-5 association with heterochromatin. Both MET-2 and CEC-5 are required for the normal lifespan of C. elegans. Furthermore, a forward genetic screening identified a conserved Arginine124 of CEC-5s chromodomain, which was essential for CEC-5s association with chromatin and life span regulation. Thus, our work will serve as a reference to explore chromodomain functions and regulation in C. elegans and allow potential applications in aging-related human diseases.

molecular biology↗