Biology subjects

Fedorov, D. A.

Publications and source records attributed to Fedorov, D. A..

3 recordsLinked to original sources

bioRxiv2025

Alteration in the intracellular Na+/K+ ratio regulates gene expression through the shift of G-quadruplex dynamics in living cells

Alteration in the intracellular Na+i/K+i ratio can play an important regulatory role in many mammalian cells. Here, we demonstrated that the expression of some early response genes does depend on the intracellular Na+i/K+i ratio and that the inhibition of DNA-binding activity of transcription factors c-Fos and c-Jun attenuates the upregulation of Zfp36 and Egr1 genes in HeLa cells. Both replacement of intracellular Na+ and K+ by Li+ and the dissipation of Na+i/K+i gradient demonstrated a similar effect on the transcription of Fos, Jun, Zfp36, and Ptgs2. Oligonucleotide sequences from the Fos, Kit, and My[c] promoters with an ability to fold into G-quadruplexes (G4s) change their conformations differently depending on the ratio of Na+, K+, and Li+ ions in vitro. Fluorescence lifetime imaging microscopy studies using DNA G4-specific dye DAOTA-M2 revealed that changes in compositions and ratios of monovalent metal cations in HeLa cells were accompanied by alterations in intranuclear G4s dynamics. The data demonstrate that these structures may be considered as intracellular sensors of monovalent metal cations regulating gene expression through the shift of G4s dynamics.

biochemistry↗

bioRxiv2025

Rapid divergence of male and female mitochondrial genomes in a basal protobranch bivalve Yoldia hyperborea

Doubly uniparental inheritance (DUI) of mitochondrial DNA (mtDNA) is a mode of mtDNA transmission whereby the male mitogenome is inherited predominately by males and the female mitogenome is inherited by females. DUI is unique to bivalve mollusks and has been identified in all major bivalve clades, including Protobranchia, the most basal bivalve subclade. Meanwhile, the mechanisms underlying the emergence and evolution of DUI remain poorly understood. Here, we focus on the early stages of divergence of male and female mitochondrial genomes by sequencing them in a basal Protobranchia species Yoldia hyperborea where they are characterized by low level of divergence, suggesting a recent origin of this system. Despite the relatively high relatedness of female and male genomes, we find that they have undergone rapid divergence both on the sequence and the structural level, including an origin of a novel gene, the ORFan, in the male genome. This novel gene is functional, as evidenced by the fact that it is transcribed and is subject to purifying selection. We show that this gene is a result of duplication and rapid evolution of another mitochondrial gene, NAD2. Additionally, the female mitogenome carries a duplicated cassette containing the cytochrome b gene, resulting in two different transcripts in female gonads both of which are subject to purifying selection, although their transcription levels differ by two orders of magnitude. These results showcase the rapid evolution of mitochondrial genes following their duplication, which occurred near the time of divergence of M- and F- mitochondrial genomes within a doubly uniparental inheritance system.

evolutionary biology↗

bioRxiv2024

Isolated human Fos promoter in plasmid DNA is overactive

Changes in intracellular concentrations of Na+ and K+ are shown to alter Fos gene expression. Here, we obtained a genetic construct encoding TurboGFP-dest1 gene under control of the human Fos promoter (-549; +155) and studied its expression in HEK293T. Amplification of the Fos promoter sequence from genomic DNA was only efficient in the presence of Li+ ions. Ouabain and medium with replacement of Na+ with Li+ ions resulted in the accumulation of Na+ and Li+ in cells, respectively. These stimuli increased the mRNA level of endogenous Fos and the average fluorescence intensity of TurboGFP-dest1 in transfected cells. The mRNA level of TurboGFP-dest1 was extremely higher than the mRNA level of endogenous Fos and was little affected by the stimuli.

molecular biology↗