Biology subjects

Sidorov, S.

Publications and source records attributed to Sidorov, S..

4 recordsLinked to original sources

bioRxiv2026

Meiotic recombination spans almost entire chromosome arms in a fully monoarmed karyotype of an African annual killifish Nothobranchius virgatus

During meiosis, homologous chromosomes pair to form synaptonemal complexes (SCs) and exchange genetic material through a process known as meiotic recombination. First, programmed DNA double-strand breaks form, followed by the assembly of recombination foci on SCs. These foci mark the sites of recombination intermediates and future crossovers. Distributions of recombination foci along SCs have been studied in many eukaryotes, revealing the interplay between recombination patterns and genome evolution. However, in fish, data on recombination patterns are scarce, and, for the majority of groups, completely absent. Here, we measure the positions of MLH1 foci in 3,504 SCs from 219 male meiotic cells of an African annual killifish Nothobranchius virgatus, a representative of a genus with remarkable karyotype and genome diversity, and present a detailed statistical analysis of its recombination patterns. We found that, in contrast to the several other fish species characterised to date, recombination in N. virgatus occurs across almost entire chromosome arms, excluding (peri)centromeres and telomeres. In the longest SCs, we observed a proximal and a distal peak of the recombination focus frequency and explained the peaks by chromosome pairing dynamics. We also revealed the typical positions of focus pairs, demonstrated interference between foci, with the minimal interfocus distance of 4 m, and described regions of the total recombination suppression near centromeres and telomeres. In sum, our study provides a detailed analysis of recombination patterns in a killifish with a fully acrocentric karyotype and contributes to cytogenomic and statistical methodology for future exploration of meiotic recombination patterns.

genetics↗

bioRxiv2024

Cross-tissue isoform switches by human transcription factors suggest a widespread regulatory mechanism

Many human genes, including transcription factor (TF) genes, produce alternative coding isoforms. Although some alternative coding TF isoforms have been experimentally studied, a genome-wide characterisation of all such isoforms in normal human physiology is still lacking. Here, we integrate RNA sequencing and protein domain data to reveal the expression levels, tissue specificity and putative functional classes of alternative coding isoforms of human TF genes. We found that isoforms lacking a DNA-binding domain (DBD) are annotated for almost a third of known TF genes, comprise 17% of all annotated TF isoforms and likely reverse the regulatory effects of DBD-containing isoforms. Considering all coding TF isoforms, we uncovered 536 switches between the highest-expressed alternative isoforms produced by 360 TF genes across 43 adult tissues. We predicted functional consequences of these switches using a functional annotation of structural domains present in switching isoforms. Furthermore, we found 45 isoform switches between the brain and non-brain tissues and interpreted six of these switches in detail. Finally, we assembled a literature-based compendium of human TF genes with experimentally studied alternative isoforms. In total, our results suggest that the switches of alternative coding TF isoforms between adult tissues represent a widespread, yet understudied, functional mechanism.

genomics↗

bioRxiv2024

Nerve-associated macrophages control adipose homeostasis across lifespan and restrain age-related inflammation

Age-related inflammation or inflammaging is a key mechanism that increases disease burden and may control lifespan. How adipose tissue macrophages (ATMs) control inflammaging is not well understood in part because the molecular identities of niche-specific ATMs are incompletely known. Using intravascular labeling to exclude circulating myeloid cells and subsequent single-cell sequencing with orthogonal validation, we define the diversity and alterations in niche resident ATMs through lifespan. Aging led to depletion of vessel-associated macrophages (VAMs), expansion of lipid-associated macrophages (LAMs), and emergence of a unique subset of CD38+ age-associated macrophages (AAMs) in visceral white adipose tissue (VAT). Interestingly, CD169+CD11c- ATMs are enriched in a subpopulation of nerve-associated macrophages (NAMs) that declines with age. Depletion of CD169+ NAMs in aged mice increases inflammaging and impairs lipolysis suggesting that they are necessary for preventing catecholamine resistance in VAT. These findings reveal specialized ATMs control adipose homeostasis and link inflammation to tissue dysfunction during aging.

immunology↗

bioRxiv2020

Epigenetic aging of classical monocytes from healthy individuals

The impact of healthy aging on molecular programming of immune cells is poorly understood. Here, we report comprehensive characterization of healthy aging in human classical monocytes, with a focus on epigenomic, transcriptomic, and proteomic alterations, as well as the corresponding proteomic and metabolomic data for plasma, using healthy cohorts of 20 young and 20 older individuals (~27 and ~64 years old on average). For each individual, we performed eRRBS-based DNA methylation profiling, which allowed us to identify a set of age-associated differentially methylated regions (DMRs) - a novel, cell-type specific signature of aging in DNA methylome. Optimized ultra-low-input ChIP-seq (ULI-ChIP-seq) data acquisition and analysis pipelines applied to 5 chromatin marks for each individual revealed lack of large-scale age-associated changes in chromatin modifications and allowed us to link hypo- and hypermethylated DMRs to distinct chromatin modification patterns. Specifically, hypermethylation events were associated with H3K27me3 in the CpG islands near promoters of lowly-expressed genes, while hypomethylated DMRs were enriched in H3K4me1 marked regions and associated with normal pattern of expression. Furthermore, hypo- and hypermethylated DMRs followed distinct functional and genetic association patterns. Hypomethylation events were associated with age-related increase of expression of the corresponding genes, providing a link between DNA methylation and age-associated transcriptional changes in primary human cells. Furthermore, these locations were also enriched in genetic regions associated by GWAS with asthma, total blood protein, hemoglobin levels and MS. On the other side, acceleration of epigenetic age in HIV and asthma stems only from changes in hypermethylated DMRs but not from hypomethylated loci.

systems biology↗