The Conserved PBAF Nucleosome-Remodeling Complex Mediates the Response to Stress in <i>Caenorhabditis elegans</i>

Kuzmanov, Aleksandra; Karina, Evguenia I.; Kirienko, Natalia V.; Fay, David S.

doi:10.1128/mcb.01502-13

Cited by 17 publications

(28 citation statements)

References 64 publications

(106 reference statements)

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“…Our two RNA sequencing datasets utilized different SWI/SNF mutants: swsn-1 encodes a core subunit that is present in all SWI/SNF complexes, while swsn-9 encodes an accessory subunit that is specific to the PBAF complex in worms (Fig. 4 a) [ 10 , 23 ]. We have an opportunity with these datasets to compare the effect of loss of different SWI/SNF subunits on gene expression.…”

Section: Resultsmentioning

confidence: 99%

SWI/SNF complexes act through CBP-1 histone acetyltransferase to regulate acute functional tolerance to alcohol

et al. 2020

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Background SWI/SNF chromatin remodeling genes are required for normal acute responses to alcohol in C. elegans and are associated with alcohol use disorder in two human populations. In an effort to discover the downstream genes that are mediating this effect, we identified SWI/SNF-regulated genes in C. elegans. Results To identify SWI/SNF-regulated genes in adults, we compared mRNA expression in wild type and swsn-1(os22ts) worms under conditions that produce inactive swsn-1 in mature cells. To identify SWI/SNF-regulated genes in neurons, we compared gene expression in swsn-9(ok1354) null mutant worms that harbor a neuronal rescue or a control construct. RNA sequencing was performed to an average depth of 25 million reads per sample using 50-base, paired-end reads. We found that 6813 transcripts were significantly differentially expressed between swsn-1(os22ts) mutants and wild-type worms and 2412 transcripts were significantly differentially expressed between swsn-9(ok1354) mutants and swsn-9(ok1354) mutants with neuronal rescue. We examined the intersection between these two datasets and identified 603 genes that were differentially expressed in the same direction in both comparisons; we defined these as SWI/SNF-regulated genes in neurons and in adults. Among the differentially expressed genes was cbp-1, a C. elegans homolog of the mammalian CBP/p300 family of histone acetyltransferases. CBP has been implicated in the epigenetic regulation in response to alcohol in animal models and a polymorphism in the human CBP gene, CREBBP, has been associated with alcohol-related phenotypes. We found that cbp-1 is required for the development of acute functional tolerance to alcohol in C. elegans. Conclusions We identified 603 transcripts that were regulated by two different SWI/SNF complex subunits in adults and in neurons. The SWI/SNF-regulated genes were highly enriched for genes involved in membrane rafts, suggesting an important role for this membrane microdomain in the acute alcohol response. Among the differentially expressed genes was cbp-1; CBP-1 homologs have been implicated in alcohol responses across phyla and we found that C. elegans cbp-1 was required for the acute alcohol response in worms.

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Section: Resultsmentioning

confidence: 99%

SWI/SNF complexes act through CBP-1 histone acetyltransferase to regulate acute functional tolerance to alcohol

et al. 2020

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“…Computational analysis of the upstream regions identified a strongly conserved, 11-nucleotide sequence ( Fig 2A ). This motif, called the ESRE [ 40 ] has been shown to work with the PBAF chromatin remodeling complex to control the response to pleiotropic abiotic stresses [ 40 – 43 ]. Statistical analysis demonstrated overrepresentation of this motif in the previously described cluster of genes strongly upregulated specifically in Liquid Killing (present in >40% of genes, p = 1.1 E-10) and in the 167 genes upregulated by Liquid Killing; but not in genes upregulated by P .…”

Section: Resultsmentioning

confidence: 99%

A conserved mitochondrial surveillance pathway is required for defense against Pseudomonas aeruginosa

Tjahjono

Kirienko

2017

PLoS Genet

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All living organisms exist in a precarious state of homeostasis that requires constant maintenance. A wide variety of stresses, including hypoxia, heat, and infection by pathogens perpetually threaten to imbalance this state. Organisms use a battery of defenses to mitigate damage and restore normal function. Previously, we described a Caenorhabditis elegans-Pseudomonas aeruginosa assay (Liquid Killing) in which toxicity to the host is dependent upon the secreted bacterial siderophore pyoverdine. Although pyoverdine is also indispensable for virulence in mammals, its cytological effects are unclear. We used genetics, transcriptomics, and a variety of pathogen and chemical exposure assays to study the interactions between P. aeruginosa and C. elegans. Although P. aeruginosa can kill C. elegans through at least 5 different mechanisms, the defense responses activated by Liquid Killing are specific and selective and have little in common with innate defense mechanisms against intestinal colonization. Intriguingly, the defense response utilizes the phylogenetically-conserved ESRE (Ethanol and Stress Response Element) network, which we and others have previously shown to mitigate damage from a variety of abiotic stresses. This is the first report of this networks involvement in innate immunity, and indicates that host innate immune responses overlap with responses to abiotic stresses. The upregulation of the ESRE network in C. elegans is mediated in part by a family of bZIP proteins (including ZIP-2, ZIP-4, CEBP-1, and CEBP-2) that have overlapping and unique functions. Our data convincingly show that, following exposure to P. aeruginosa, the ESRE defense network is activated by mitochondrial damage, and that mitochondrial damage also leads to ESRE activation in mammals. This establishes a role for ESRE in a phylogenetically-conserved mitochondrial surveillance system important for stress response and innate immunity.

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“…A functional fusion between the nekl-2 gene and mCherry sequences was generated using a modified pPD95.77 vector in which GFP sequences have been replaced by mCherry (Kuzmanov et al, 2014). A 1,888-kb nekl-2 genomic fragment containing 891 bp of 5' flanking DNA was obtained following PCR amplification using a rescuing fosmid clone, WRM0639aE11, as template using primers NEKL2Ch1 and NEKL2Ch2.…”

Section: Methodsmentioning

confidence: 99%

C. elegans NIMA-related kinases NEKL-2 and NEKL-3 are required for the completion of molting

Yochem

Lažetić

Bell

et al. 2015

Developmental Biology

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C. elegans molting is a process during which the apical extracellular matrix of the epidermis, the cuticle, is remodeled through a process of degradation and re-synthesis. Using a genetic approach, we identified nekl-3 as essential for the completion of molting. NEKL-3 is highly similar to the mammalian NEK kinase family members NEK6 and NEK7. Animals homozygous for a hypomorphic mutation in nekl-3, sv3, had a novel molting defect in which the central body region, but not the head or tail, was unable to shed the old cuticle. In contrast, a null mutation in nekl-3, gk506, led to complete enclosure within the old cuticle. nekl-2, which is most similar to mammalian NEK8, was also essential for molting. Mosaic analyses demonstrated that NEKL-2 and NEKL-3 were specifically required within the large epidermal syncytium, hyp7, to facilitate molting. Consistent with this, NEKL-2 and NEKL-3 were expressed at the apical surface of hyp7 where they localized to small spheres or tubular structures. Inhibition of nekl-2, but not nekl-3, led to the mislocalization of LRP-1/megalin, a cell surface receptor for low-density lipoprotein (LDL)-binding proteins. In addition, nekl-2 inhibition led to the mislocalization of several other endosome-associated proteins. Notably, LRP-1 acts within hyp7 to facilitate completion of molting, suggesting at least one mechanism by which NEKL-2 may influence molting. Notably, our studies failed to reveal a requirement for NEKL-2 or NEKL-3 in cell division, a function reported for several mammalian NEKs including NEK6 and NEK7. Our findings provide the first genetic and in vivo evidence for a role of NEK family members in endocytosis, which may be evolutionarily conserved.

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The Conserved PBAF Nucleosome-Remodeling Complex Mediates the Response to Stress in Caenorhabditis elegans

Cited by 17 publications

References 64 publications

SWI/SNF complexes act through CBP-1 histone acetyltransferase to regulate acute functional tolerance to alcohol

SWI/SNF complexes act through CBP-1 histone acetyltransferase to regulate acute functional tolerance to alcohol

A conserved mitochondrial surveillance pathway is required for defense against Pseudomonas aeruginosa

C. elegans NIMA-related kinases NEKL-2 and NEKL-3 are required for the completion of molting

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