scholarly journals Overlapping and non-overlapping roles of the class-I histone deacetylase-1 corepressors, LET-418, SIN-3, and SPR-1 in Caenorhabditis elegans embryonic development

2020 ◽  
Author(s):  
Yukihiro Kubota ◽  
Yuto Ohnishi ◽  
Tasuku Hamasaki ◽  
Gen Yasui ◽  
Natsumi Ota ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Embryonic Development ◽  
Histone Deacetylases ◽  
Class I ◽  
Biological Processes ◽  
Nucleosome Remodeling ◽  
C Elegans ◽  
Histone Deacetylase 1 ◽  
Genome Wide ◽  
Sin3 Complex

AbstractHistone deacetylases (HDACs) are divided into four classes. Class-I HDAC, HDAC-1 forms three types of complexes, namely the Nucleosome Remodeling Deacetylase complex, the Sin3 complex, and the CoREST complex, with specific corepressor component Mi2/CHD-3, Sin3, and RCOR1 in human, respectively. The functions of these HDAC-1 complexes are regulated by their corepressors, however, their exact mechanistic roles in several biological processes remain unexplored, such as in embryonic development. Here, we report that each of the corepressors, LET-418, SIN-3, and SPR-1, the homologous of Mi2, Sin3, and RCOR1, respectively, were expressed throughout Caenorhabditis elegans embryonic development and served essential roles in the process. Moreover, genetic analysis suggested that three pathways (i.e., LET-418– SIN-3–SPR-1, SIN-3–SPR-1, and LET-418) participated in embryonic development. Our terminal-phenotype observations of single mutants of each corepressor implied that LET-418, SIN-3, and SPR-1 played similar roles in promoting advancement to the middle and late embryonic stages. Genome-wide comparative-transcriptome analysis indicated that 47.5% and 42.3% of genes were commonly increased and decreased in sin-3 and spr-1 mutants, respectively. These results suggest that among the three pathways studied, the SIN-3–SPR-1 pathway mainly serves to regulate embryonic development. Comparative-Gene Ontology analysis indicated that these three pathways played overlapping and distinct roles in regulating C. elegans embryonic development.

scholarly journals Overlapping and non-overlapping roles of the class-I histone deacetylase-1 corepressors LET-418, SIN-3, and SPR-1 in Caenorhabditis elegans embryonic development

2021 ◽  
Author(s):  
Yukihiro Kubota ◽  
Yuto Ohnishi ◽  
Tasuku Hamasaki ◽  
Gen Yasui ◽  
Natsumi Ota ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Embryonic Development ◽  
Histone Deacetylase ◽  
Genetic Interactions ◽  
Class I ◽  
Specific Cell ◽  
Nucleosome Remodeling ◽  
Expression Levels ◽  
C Elegans ◽  
Functional Relationships

AbstractBackgroundHistone deacetylase (HDAC)-1, a Class-I HDAC family member, forms three types of complexes, the nucleosome remodeling deacetylase, Sin3, and CoREST complexes with the specific corepressor components chromodomain-helicase-DNA-binding protein 3 (Mi2/CHD-3), Sin3, and REST corepressor 1 (RCOR1), respectively, in humans.ObjectiveTo elucidate the functional relationships among the three transcriptional corepressors during embryogenesis.MethodsThe activities of HDA-1, LET-418, SIN-3, and SPR-1, the homologs of HDAC-1, Mi2, Sin3, and RCOR1 inCaenorhabditis elegansduring embryogenesis were investigated through measurement of relative mRNA expression levels and embryonic lethality given either gene knockdown or deletion. Additionally, the terminal phenotypes of each knockdown and mutant embryo were observed using a differential-interference contrast microscope. Finally, the functional relationships among the three corepressors were examined through genetic interactions and transcriptome analyses.ResultsHere, we report that each of the corepressors LET-418, SIN-3, and SPR-1 are expressed and have essential roles inC. elegansembryonic development. Our terminal phenotype observations of single mutants further implied that LET-418, SIN-3, and SPR-1 play similar roles in promoting advancement to the middle and late embryonic stages. Combined analysis of genetic interactions and gene ontology of these corepressors indicate a prominent overlapping role among SIN-3, SPR-1, and LET-418 and between SIN-3 and SPR-1.ConclusionOur findings suggest that the class-I HDAC-1 corepressors LET-418, SIN-3, and SPR-1 may cooperatively regulate the expression levels of some genes duringC. elegansembryogenesis or may have some similar roles but functioning independently within a specific cell.

scholarly journals The worm's turn: Genome-wide RNAi in Caenorhabditis elegans

2004 ◽  
Vol 26 (5) ◽  
pp. 25-28
Author(s):  
Gino Poulin ◽  
David P. Welchman
Keyword(s):  
Caenorhabditis Elegans ◽  
New Technology ◽  
Biological Processes ◽  
Systematic Screening ◽  
C Elegans ◽  
Genome Wide ◽  
Powerful Approach ◽  
Gene Functions ◽  
New Gene ◽  
Multiple Species

RNAi-mediated silencing is now being used in multiple species, from plants to humans, to identify gene functions. This new technology is fully exploited in Caenorhabditis elegans, since an RNAi feeding library that has the potential to inactivate 86% of the predicted genes of the C. elegans genome is publicly available. This tool made systematic screening of genes involved in biological processes of interest easier, but there are some pitfalls: specificity, reproducibility and hypomorphic effects. However, as with any other technology, RNAi is getting better as time goes on. Once these caveats are taken into account, RNAi-mediated silencing is still a very powerful approach to identify new gene functions and to dissect complex pathways.

scholarly journals Functional Requirement for Histone Deacetylase 1 in Caenorhabditis elegans Gonadogenesis

2002 ◽  
Vol 22 (9) ◽  
pp. 3024-3034 ◽  
Author(s):  
Pascale Dufourcq ◽  
Martin Victor ◽  
Frédérique Gay ◽  
Dominica Calvo ◽  
Jonathan Hodgkin ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Histone Deacetylase ◽  
Histone Deacetylases ◽  
Regulation Of Gene Expression ◽  
Notch Signaling Pathway ◽  
Transcriptional Repressors ◽  
Vulval Development ◽  
C Elegans ◽  
Histone Deacetylase 1 ◽  
Multicellular Organisms

ABSTRACT Histone acetylation and deacetylation have been implicated in the regulation of gene expression. Molecular studies have shown that histone deacetylases (HDACs) function as transcriptional repressors. However, very little is known about their roles during development in multicellular organisms. We previously demonstrated that inhibition of maternal and zygotic expression of histone deacetylase 1 (HDA-1) causes embryonic lethality in Caenorhabditis elegans. Here, we report the identification of an hda-1 genetic mutant which has also been called a gon-10 mutant (for gonadogenesis defective 10) and show that loss of HDA-1 zygotic expression results in specific postembryonic defects in gonadogenesis and vulval development. We provide evidence that the lag-2 gene, which plays a role in gonadogenesis and vulval development and encodes a Notch ligand, is derepressed in gon-10 animals, suggesting that lag-2 may be a target of HDA-1. Our findings reveal a novel and specific function for the ubiquitously expressed HDA-1 in C. elegans gonadogenesis and place hda-1 in the Notch signaling pathway.

scholarly journals The conserved histone chaperone LIN-53 links lifespan and healthspan regulation in Caenorhabditis elegans

2019 ◽  
Author(s):  
Stefanie Müthel ◽  
Bora Uyar ◽  
Mei He ◽  
Anne Krause ◽  
Burcu Vitrinel ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Memory Loss ◽  
Histone Chaperone ◽  
Premature Aging ◽  
Biological Processes ◽  
Nurd Complex ◽  
Metabolome Analysis ◽  
Nucleosome Remodeling ◽  
C Elegans ◽  
Evolutionarily Conserved

SummaryWhether extension of lifespan provides an extended time without health deteriorations is an important issue for human aging. However, to which degree lifespan and healthspan regulation might be linked is not well understood. Chromatin factors could be involved in linking both aging aspects, as epigenetic mechanisms bridge regulation of different biological processes. The epigenetic factor LIN-53 (RBBP4/7) is required for safeguarding cell identities in Caenorhabditis elegans as well as mammals and for preventing memory loss and premature aging in humans. LIN-53 is a histone chaperone that associates with different chromatin-regulating complexes. We show that LIN-53 interacts with the Nucleosome remodeling and deacteylase (NuRD)-complex in C. elegans muscles to promote healthy locomotion during aging. While mutants for other NuRD members show a normal lifespan, animals lacking LIN-53 die early because LIN-53 depletion affects also the Histone deacetylase complex Sin3, which is required for a normal lifespan. To determine why lin-53 and sin-3 mutants die early, we performed transcriptome and metabolome analysis and found that levels of the disaccharide Trehalose are significantly decreased in both mutants. As Trehalose is required for normal lifespan in C. elegans, lin-53 and sin-3 mutants could be rescued by either feeding with Trehalose or increasing Trehalose levels via the Insulin/IGF1 signaling pathway. Overall, our findings suggest that LIN-53 is required for maintaining lifespan and promoting healthspan through discrete chromatin regulatory mechanisms. Since both LIN-53 and its mammalian homologs safeguard cell identities, it is conceivable that its implication in lifespan and healthspan regulation is also evolutionarily conserved.

scholarly journals Natural variation in fecundity is correlated with species-wide levels of divergence in Caenorhabditis elegans

2021 ◽  
Author(s):  
Gaotian Zhang ◽  
Jake D Mostad ◽  
Erik C Andersen
Keyword(s):  
Life History ◽  
Caenorhabditis Elegans ◽  
Life History Traits ◽  
Life History Trait ◽  
Selective Sweeps ◽  
C Elegans ◽  
Genome Wide ◽  
Genetic Complexity ◽  
Genomic Regions ◽  
Global Population

Abstract Life history traits underlie the fitness of organisms and are under strong natural selection. A new mutation that positively impacts a life history trait will likely increase in frequency and become fixed in a population (e.g. a selective sweep). The identification of the beneficial alleles that underlie selective sweeps provides insights into the mechanisms that occurred during the evolution of a species. In the global population of Caenorhabditis elegans, we previously identified selective sweeps that have drastically reduced chromosomal-scale genetic diversity in the species. Here, we measured the fecundity of 121 wild C. elegans strains, including many recently isolated divergent strains from the Hawaiian islands and found that strains with larger swept genomic regions have significantly higher fecundity than strains without evidence of the recent selective sweeps. We used genome-wide association (GWA) mapping to identify three quantitative trait loci (QTL) underlying the fecundity variation. Additionally, we mapped previous fecundity data from wild C. elegans strains and C. elegans recombinant inbred advanced intercross lines that were grown in various conditions and detected eight QTL using GWA and linkage mappings. These QTL show the genetic complexity of fecundity across this species. Moreover, the haplotype structure in each GWA QTL region revealed correlations with recent selective sweeps in the C. elegans population. North American and European strains had significantly higher fecundity than most strains from Hawaii, a hypothesized origin of the C. elegans species, suggesting that beneficial alleles that caused increased fecundity could underlie the selective sweeps during the worldwide expansion of C. elegans.

scholarly journals Effects of NAD+ in Caenorhabditis elegans Models of Neuronal Damage

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 993
Author(s):  
Yuri Lee ◽  
Hyeseon Jeong ◽  
Kyung Hwan Park ◽  
Kyung Won Kim
Keyword(s):  
Caenorhabditis Elegans ◽  
Therapeutic Strategy ◽  
Axon Regeneration ◽  
Neuronal Damage ◽  
Biological Processes ◽  
Nematode Caenorhabditis Elegans ◽  
C Elegans ◽  
Neuronal Functions ◽  
Molecular Components

Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor that mediates numerous biological processes in all living cells. Multiple NAD+ biosynthetic enzymes and NAD+-consuming enzymes are involved in neuroprotection and axon regeneration. The nematode Caenorhabditis elegans has served as a model to study the neuronal role of NAD+ because many molecular components regulating NAD+ are highly conserved. This review focuses on recent findings using C. elegans models of neuronal damage pertaining to the neuronal functions of NAD+ and its precursors, including a neuroprotective role against excitotoxicity and axon degeneration as well as an inhibitory role in axon regeneration. The regulation of NAD+ levels could be a promising therapeutic strategy to counter many neurodegenerative diseases, as well as neurotoxin-induced and traumatic neuronal damage.

scholarly journals Signaling by AWC Olfactory Neurons Is Necessary for Caenorhabditis elegans’ Response to Prenol, an Odor Associated with Nematode-Infected Insects

Genetics ◽  
2020 ◽  
Vol 216 (1) ◽  
pp. 145-157
Author(s):  
Tiffany Baiocchi ◽  
Kyle Anesko ◽  
Nathan Mercado ◽  
Heenam Park ◽  
Kassandra Kin ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Behavioral Ecology ◽  
Natural Variation ◽  
Isoamyl Alcohol ◽  
Life Cycles ◽  
C Elegans ◽  
Link Type ◽  
Genome Wide ◽  
Ecological Differences

Chemosensation plays a role in the behaviors and life cycles of numerous organisms, including nematodes. Many guilds of nematodes exist, ranging from the free-living Caenorhabditis elegans to various parasitic species such as entomopathogenic nematodes (EPNs), which are parasites of insects. Despite ecological differences, previous research has shown that both EPNs and C. elegans respond to prenol (3-methyl-2-buten-1-ol), an odor associated with EPN infections. However, it is unclear how C. elegans responds to prenol. By utilizing natural variation and genetic neuron ablation to investigate the response of C. elegans to prenol, we found that the AWC neurons are involved in the detection of prenol and that several genes (including dcap-1, dcap-2, and clec-39) influence response to this odorant. Furthermore, we identified that the response to prenol is mediated by the canonically proposed pathway required for other AWC-sensed attractants. However, upon testing genetically diverse isolates, we found that the response of some strains to prenol differed from their response to isoamyl alcohol, suggesting that the pathways mediating response to these two odorants may be genetically distinct. Further, evaluations leveraging natural variation and genome wide association revealed specific genes that influence nematode behavior and provide a foundation for future studies to better understand the role of prenol in nematode behavioral ecology.

The C. elegans septin genes, unc-59 and unc-61, are required for normal postembryonic cytokineses and morphogenesis but have no essential function in embryogenesis

2000 ◽  
Vol 113 (21) ◽  
pp. 3825-3837 ◽  
Author(s):  
T.Q. Nguyen ◽  
H. Sawa ◽  
H. Okano ◽  
J.G. White
Keyword(s):  
Caenorhabditis Elegans ◽  
Embryonic Development ◽  
Sensory Neurons ◽  
Leading Edge ◽  
The Other ◽  
Male Tail ◽  
Genomic Database ◽  
C Elegans ◽  
Essential Function ◽  
Normal Embryonic Development

Septins have been shown to play important roles in cytokinesis in diverse organisms ranging from yeast to mammals. In this study, we show that both the unc-59 and unc-61 loci encode Caenorhabditis elegans septins. Genomic database searches indicate that unc-59 and unc-61 are probably the only septin genes in the C. elegans genome. UNC-59 and UNC-61 localize to the leading edge of cleavage furrows and eventually reside at the midbody. Analysis of unc-59 and unc-61 mutants revealed that each septin requires the presence of the other for localization to the cytokinetic furrow. Surprisingly, unc-59 and unc-61 mutants generally have normal embryonic development; however, defects were observed in post-embryonic development affecting the morphogenesis of the vulva, male tail, gonad, and sensory neurons. These defects can be at least partially attributed to failures in post-embryonic cytokineses although our data also suggest other possible roles for septins. unc-59 and unc-61 double mutants show similar defects to each of the single mutants.

scholarly journals Regulating the Regulators: The Role of Histone Deacetylase 1 (HDAC1) in Erythropoiesis

2020 ◽  
Vol 21 (22) ◽  
pp. 8460
Author(s):  
Min Young Kim ◽  
Bowen Yan ◽  
Suming Huang ◽  
Yi Qiu
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Histone Deacetylase ◽  
Histone Deacetylases ◽  
Gene Activation ◽  
Bhlh Transcription Factor ◽  
Nucleosome Remodeling ◽  
Hdac Activity ◽  
Histone Deacetylase 1

Histone deacetylases (HDACs) play important roles in transcriptional regulation in eukaryotic cells. Class I deacetylase HDAC1/2 often associates with repressor complexes, such as Sin3 (Switch Independent 3), NuRD (Nucleosome remodeling and deacetylase) and CoREST (Corepressor of RE1 silencing transcription factor) complexes. It has been shown that HDAC1 interacts with and modulates all essential transcription factors for erythropoiesis. During erythropoiesis, histone deacetylase activity is dramatically reduced. Consistently, inhibition of HDAC activity promotes erythroid differentiation. The reduction of HDAC activity not only results in the activation of transcription activators such as GATA-1 (GATA-binding factor 1), TAL1 (TAL BHLH Transcription Factor 1) and KLF1 (Krüpple-like factor 1), but also represses transcription repressors such as PU.1 (Putative oncogene Spi-1). The reduction of histone deacetylase activity is mainly through HDAC1 acetylation that attenuates HDAC1 activity and trans-repress HDAC2 activity through dimerization with HDAC1. Therefore, the acetylation of HDAC1 can convert the corepressor complex to an activator complex for gene activation. HDAC1 also can deacetylate non-histone proteins that play a role on erythropoiesis, therefore adds another layer of gene regulation through HDAC1. Clinically, it has been shown HDACi can reactivate fetal globin in adult erythroid cells. This review will cover the up to date research on the role of HDAC1 in modulating key transcription factors for erythropoiesis and its clinical relevance.

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