Biology subjects

Pletenev, I. A.

Publications and source records attributed to Pletenev, I. A..

4 recordsLinked to original sources

bioRxiv2026

Accelerated Aging Signatures in 3D Genome Organization and Transcriptome in Schizophrenia

Schizophrenia is a severe neuropsychiatric disorder that affects the behavioral, emotional and cognitive state of patients. Despite its substantial heritability, the molecular etiology of the disease remains poorly understood. Many schizophrenia-associated genetic variants reside in non-coding regions, and exert their effects through distal regulatory elements of the genome. In this context, the three-dimensional organization of the genome is expected to play a decisive role in establishing contacts between these regulatory elements and their target genes, thereby mediating schizophrenia-associated dysregulation of gene expression. Here, we present a novel Hi-C dataset providing an unprecedented view of three-dimensional genome organization in post-mortem schizophrenia brain samples. Our findings indicate that most changes occur at long-range genomic distances while local architecture of topologically-associated domains remains largely intact. However, neurons display localized and functionally relevant loop differences, particularly in regulatory regions associated with neurodevelopmental processes. Global characteristics of higher-order chromatin organization show accelerated aging alteration pattern in schizophrenia, and downstream analysis of transcriptomic data in schizophrenia brain samples further confirms that schizophrenia is associated with accelerated aging.

bioinformatics↗

bioRxiv2025

Ultra-long-range Polycomb-coupled interactions underlie subtype identity of human cortical neurons

Regulation of gene expression by Polycomb group (PcG) proteins orchestrates neural development and cell-type specification. However, the mechanisms by which neural progenitor cells diversify into the myriad cell types of the human brain remain poorly understood. Here, we investigate the role of Polycomb pro-teins in shaping the single-cell 3D genome, transcriptome, and chromatin binding landscape of the developing and adult human cortex. We show that PcG proteins establish a network of long-range repressive interactions encompassing loci with neuronal marker genes. These interactions occur in a neuron-type-dependent manner, selectively targeting genes that must remain silenced in a given cell type. These interactions are present in fetal neurons and increase markedly in strength after birth. Our results highlight PcG proteins as key regulators of neuronal cell fate specification in the human brain.

genomics↗

bioRxiv2024

Convergent gene pairs restrict chromatin looping in Dictyostelium discoideum, acting as directional barriers for extrusion

Dictyostelium discoideum is a unicellular slime mold, developing into a multicellular fruiting body upon starvation. Development is accompanied by large-scale shifts in gene expression program, but underlying features of chromatin spatial organization remain unknown. Here, we report that the Dictyostelium 3D genome is organized into positionally conserved, largely consecutive, non-hierarchical and weakly insulated loops at the onset of multicellular development. The transcription level within the loop interior tends to be higher than in adjacent regions. Loop interiors frequently contain functionally linked genes and genes which coherently change expression level during development. Loop anchors are predominantly positioned by the genes in convergent orientation. Our data suggest that the loop profile may arise from the interplay between transcription and extrusion-driven chromatin folding. In particular, a convergent gene pair serves as a bidirectional extrusion barrier or a "diode" that controls passage of the cohesin extruder by relative transcription level of paired genes.

molecular biology↗

bioRxiv2023

Extensive long-range polycomb interactions and weak compartmentalization are hallmarks of human neuronal 3D genome

Chromatin architecture regulates gene expression and shapes cellular identity, particularly in neuronal cells. Specifically, polycomb group (PcG) proteins enable establishment and maintenance of neuronal cell type by reorganizing chromatin into repressive domains that limit the expression of fate-determining genes and sustain distinct gene expression patterns in neurons. Here, we map the 3D genome architecture in neuronal and non-neuronal cells isolated from the Wernickes area of four human brains and comprehensively analyze neuron-specific aspects of chromatin organization. We find that genome segregation into active and inactive compartments is greatly reduced in neurons compared to other brain cells. Furthermore, neuronal Hi-C maps reveal strong long-range interactions, forming a specific network of PcG-mediated contacts in neurons that is nearly absent in other brain cells. These interacting loci contain developmental transcription factors with repressed expression in neurons and other mature brain cells. But only in neurons, they are rich in bivalent promoters occupied by H3K4me3 histone modification together with H3K27me3, which points to a possible functional role of PcG contacts in neurons. Importantly, other layers of chromatin organization also exhibit a distinct structure in neurons, characterized by an increase in short-range interactions and a decrease in long-range ones.

genomics↗