Biology subjects

Nesterova, T.

Publications and source records attributed to Nesterova, T..

3 recordsLinked to original sources

bioRxiv2026

Disentangling polymer confinement from specific-folding interactions reveals the drivers of E. coli chromosome organization

The three-dimensional organization of the bacterial chromosome is critical for gene regulation. Chromosome conformation capture (Hi-C) has enabled genome-wide mapping of chromosomal folding, yet ensemble-averaged contact maps entangle biologically specific-folding interactions (SFIs) with nonspecific polymer compaction and mask single-cell heterogeneity. Here, we developed a polymer-based simulation framework in E. coli to address these limitations. We found that a null model of 300,000 random polymer configurations recapitulated the global chromosomal organization observed in Hi-C data, establishing that most Hi-C signals reflect generic polymer behavior in a confined volume. Contrasting null-model predictions with experimental Hi-C data isolated a small subset of SFIs (< 7%) and generated a specific-fold ensemble of 20,000 single-cell conformations that reproduced chromosomal interaction domains and single-cell heterogeneity. SFIs were enriched in the ter region, reduced nucleoid accessibility, colocalized with cryptic prophages, and depleted in positively supercoiled regions. H-NS and MatP emerged as major chromosome-wide and local determinants of SFIs, respectively. Furthermore, high-SFI regions correlated with stress-adaptive genes, whereas low-SFI regions harbored housekeeping genes. Together, our results established that a small number of biologically encoded SFIs superimposed on a polymer background shape the E. coli chromosome and gene expression, providing a quantitative framework for dissecting chromosome architecture and function.

genomics↗

bioRxiv2024

FtsZ-mediated spatial-temporal control over septal cell wall synthesis

FtsZ, the tubulin-like GTPase, is the central organizer of the bacterial divisome, a macromolecular complex that synthesizes new septal cell wall and degrades old septal cell wall (made of septal peptidoglycan, sPG) to allow cell wall constriction and cytokinesis. In E. coli, it is well accepted that 1) FtsZ recruits all essential divisome proteins to the septum, including the core sPG synthase complex, FtsWI/QLB and its activator, FtsN; 2) FtsWI/QLB must complex with FtsN to produce sPG under the wild-type background; and 3) the Brownian ratcheting by treadmilling FtsZ polymers drives the directional movements of sPG synthase proteins along the septum circumference; and 4) FtsZ is essential for the early stage, but dispensable for the late stage of cell wall constriction. However, it remains unclear how FtsZ spatial-temporally organizes the divisome for robust bacterial cytokinesis throughout cell wall constriction process. Combining theoretical modeling with experiments in E. coli, we show that at the early stage during cell division, the Brownian ratcheting by FtsZ treadmilling acts both as a template to corral FtsWI/QLB and FtsN into close contacts for FtsWI/QLB-FtsN complex formation and as a conveyor to maximally homologize the septal distribution of sPG synthesis activities to avoid uneven cell wall constriction. When the septum constricts progressively, the FtsN septal density increases via binding to denuded sPG; consequently, the denuded PG-bound FtsN serves as the template to activate FtsWI/QLB for continued sPG synthesis, rendering FtsZ dispensable. Our work establishes an overarching framework that FtsZ spatial-temporally controls over septal cell wall constriction. SignificanceBacteria utilize FtsZ, the tubulin-like GTPase, to organize cell wall enzymes during cell division. FtsZ forms treadmilling polymers along the septum circumference and drives the directional movement of cell wall enzymes for robust cell wall constriction. How this role is achieved is unclear. We show that FtsZ treadmilling acts both as a template to corral cell wall enzymes into close contacts for priming and as a conveyor to homologize the septal distribution of cell wall synthesis activities for even septum constriction. These roles evolve at different stages of cell division and are modulated differentially by different bacteria; they likely define an overarching principle for robust cell division across the microbial world.

biophysics↗

bioRxiv2023

YY1 binding is a gene-intrinsic barrier to Xist-mediated gene silencing

X chromosome inactivation (XCI) in mammals is mediated by Xist RNA which functions in cis to silence genes on a single X chromosome in XX female cells, thereby equalising levels of X-linked gene expression relative to XY males. XCI progresses over a period of several days, with some X-linked genes silencing faster than others. Chromosomal location of a gene is an important determinant of silencing rate, but uncharacterised gene-intrinsic features also mediate resistance or susceptibility to silencing. In this study, we integrate time-course data of gene silencing and decreasing inactive X (Xi) chromatin accessibility in mouse embryonic stem cell lines with an inducible Xist allele (iXist-ChrX mESCs). Our analysis reveals that motifs bound by the transcription factor YY1 are associated with persistently accessible regulatory elements, including many promoters and enhancers of slow-silencing genes. We further show that YY1 is evicted relatively slowly from target sites on Xi, and that silencing of X-linked genes is increased upon YY1 degradation. Together our results indicate that YY1 acts as barrier to Xist-mediated silencing that is removed only at late stages of the XCI process.

genomics↗