Biology subjects

Dever, K.

Publications and source records attributed to Dever, K..

4 recordsLinked to original sources

bioRxiv2024

Comparison of Infinium MethylationEPIC v2.0 to v1.0 for human population epigenetics: considerations for addressing EPIC version differences in DNA methylation-based tools

The recently launched Illumina Infinium MethylationEPIC v2.0 (EPICv2), successor of MethylationEPIC v1.0 (EPICv1), retains a majority of probes in EPICv1, while expanding coverage of regulatory elements. The concordance between the two EPIC versions in DNA methylation-based tools has not yet been investigated. To address this, DNA methylation was profiled on both versions using matched blood samples across four cohorts spanning early to late adulthood. High concordance between versions at the array level but variable agreement at the individual probe level was noted. A significant contribution of EPIC version to DNA methylation variation was observed, though it was to a smaller extent compared to sample relatedness and cell type composition. Modest but significant differences in DNA methylation-based estimates between versions were observed, irrespective of the data preprocessing method used. Adjustments for EPIC version or calculation of estimates separately for each version largely mitigated these version-specific discordances. This work emphasizes the importance of accounting for EPIC version differences in research scenarios, especially in meta-analyses and longitudinal studies that require data harmonization across versions. Summary blurbOur work illustrates the importance of accounting for EPIC version in DNA methylation-based tools, specifically in research scenarios when samples profiled across different versions are harmonized.

genomics↗

bioRxiv2021

Cdk8 directly regulates glycolysis via phosphorylation of Gcr2

CDK8 encodes an evolutionarily conserved Mediator complex kinase subunit that functions in general and context-specific transcription regulation by phosphorylating core components of the transcription machinery and gene-specific transcription factors. To better understand the role Cdk8 in transcription regulation, we performed high-resolution gene expression time course analysis following nuclear depletion of Cdk8. Focusing on the earliest gene expression alterations revealed dysregulation of genes encoding glycolysis enzymes, suggesting a functional link to Gcr1 and Gcr2, key transcriptional activators of these genes. Consistently, we found that nuclear depletion of Cdk8 altered the mRNA levels of glycolysis genes as well as the promoter occupancy of Gcr2, but not Gcr1. Examination of the Gcr2 protein sequence revealed a putative Cdk8 phosphorylation site at serine 365, which we confirmed using in vitro and in vivo assays. Importantly, phospho-mutant GCR2 recapitulated the growth and gene expression defects of the GCR2 deletion mutant, effects not observed with a phospho mimetic mutant. As such, our work highlights Gcr2 as a new Cdk8 substrate, revealing that its phosphorylation is critical for the activation of genes encoding glycolysis enzymes.

molecular biology↗

bioRxiv2020

Analysis of the oxidative stress regulon identifies soxS as a genetic target for resistance reversal in multi-drug resistant Klebsiella pneumoniae

In bacteria, the defense system deployd to counter oxidative stress is orchestrated by three transcriptional factors - SoxS, SoxR, and OxyR. Although the regulon that these factors control is known in many bacteria, similar data is not available for Klebsiella pneumoniae. To address this data gap, oxidative stress was artificially induced in K. pneumoniae MGH 78578 using paraquat and the corresponding oxidative stress regulon recorded using RNA-seq. The soxS gene was significantly induced during oxidative stress and a knock-out mutant was constructed, to explore its functionality. The wild-type and mutant were grown in the presence of paraquat and subjected to RNA-seq to elucidate the soxS regulon in K. pneumoniae MGH78578. Genes that are commonly regulated both in the oxidative stress regulon and soxS regulon were identified and denoted as the oxidative SoxS regulon - these included a stringent group of genes specifically regulated by SoxS. Efflux pump encoding genes such as acrAB-tolC, acrE, and global regulators such as marRAB were identified as part of this regulon. Consequently, the isogenic soxS mutant was found to exhibit a reduction in the minimum bactericidal concentration against tetracycline compared to that of the wild type. Impaired efflux activity, allowing tetracycline to be accumulated in the cytoplasm to bactericidal levels, was further evaluated using a tetraphenylphosphonium (TPP+) accumulation assay. The soxS mutant was also susceptible to tetracycline in vivo, in a zebrafish embryo model. We conclude that the soxS gene could be considered as a genetic target against which an inhibitor could be developed in the future and used in combinatorial therapy with tetracycline to combat infections associated with multi-drug resistant K. pneumoniae.

microbiology↗

bioRxiv2019

Social tolerance in Octopus laqueus - a maximal entropy model

Octopus laqueus is a small tropical octopus found in Okinawa, Japan and the greater Indo-Pacific. Octopus are often viewed as solitary animals but O. laqueus live in close proximity in the wild, and will potentially encounter one another on a regular basis, raising the possibility of sociality in the species. To test for social tolerance and social repulsion in O. laqueus, animals were kept in communal tanks, and the number of dens and sex composition was varied per tank, with a set mixture of sizes and with den occupancy tracked per individual. We found that O. laqueus will socially tolerate other individuals by sharing tanks and dens, including several animals in contact and sharing a den under den-limited conditions, and with typically no loss to cannibalism or escape. However, animals also exhibit significant levels of social repulsion, and individuals often chose a solitary den when given the option. The patterns of den occupancy are observed to be consistent with a maximum entropy model. Overall, the preference to have a den is stronger than the preference to be solitary in O. laqueus, and the animals are socially tolerant of others in the tank and in a den or shelter, a first for octopuses outside mating. The relaxed disposition and social tolerance of O. laqueus make it a promising species to work with in lab, and for development into a genetic model for social behavior in octopuses.

animal behavior and cognition↗