Biology subjects

Chowdhary, S.

Publications and source records attributed to Chowdhary, S..

6 recordsLinked to original sources

bioRxiv2026

Chaperone condensates buffer the heat shock response against pleiotropic inputs

Stress response pathways can be specific, dedicated to one stimulus, or pleiotropic, funneling distinct perturbations into a shared program. The heat shock response (HSR), the Hsf1-driven transcriptional program, has been linked to numerous stresses, suggesting it is pleiotropic. Here we find that high amplitude HSR activation is specific to heat shock in budding yeast. Heat shock activates the HSR through a condensate cascade in which orphan ribosomal proteins condense with Sis1 and Hsp70, titrating these chaperones away from their repressive interactions with Hsf1, triggering Hsf1 condensation with the transcriptional machinery, and activating HSR genes. Other stressors likewise drive Sis1 and Hsp70 condensation, redeploying Sis1 to stimulus-specific subcellular sites. However, chaperone condensation is not sufficient to activate the HSR. Sis1 and Hsp70 condense under conditions in which the HSR remains inactive, and Sis1 depletion increases HSR activation under all conditions except heat shock. These results suggest that chaperone condensates buffer the HSR, setting a threshold for activation and imparting specificity.

cell biology↗

bioRxiv2025

Mitochondrial fission regulates ROS for ventral furrow formation in Drosophila gastrulation

Mitochondrial dynamics are vital for embryogenesis, but their role in morphogenesis is largely unexplored. In this study, we elucidate the role of mitochondrial dynamics and function in regulating apical constriction at the ventral furrow in Drosophila gastrulation. We find that spatiotemporal redistribution of mitochondria from basal to apically constricting regions is coincident with Myosin II accumulation in ventral epithelial cells. This apical enrichment depends on intact microtubules and is regulated by Dorsal/NFkb signaling pathway. Embryos expressing mitochondrial fission protein, Drp1 mutants, contain larger, basally accumulated mitochondria, decreased apical constriction and ventral furrow defects. Transcriptomic and proteomic profiling of Drp1 mutants shows no change in Dorsal signaling, but an upregulation of antioxidant enzymes, decreased respiratory complexes, and reduced reactive oxygen species (ROS), confirming loss of mitochondrial activity and a reduced environment. Depleting mitochondrial SOD2 in Drp1 mutant embryos restores levels of antioxidant proteins and increases ROS, leading to an oxidized environment. These embryos also show rescue in apical mitochondrial migration and Myosin II accumulation, thereby enabling proper ventral furrow formation. Our study reveals the functional importance of localized mitochondrial dynamics, regulated by the Dorsal signaling pathway, and mitochondrial activity in a spatiotemporal manner for apical constriction during gastrulation.

developmental biology↗

bioRxiv2025

Emergent 3D genome reorganization from the stepwise assembly of transcriptional condensates

Transcriptional condensates are clusters of transcription factors, coactivators, and RNA Pol II associated with high-level gene expression, yet how they assemble and function within the cell remains unclear. Here we show that transcriptional condensates form in a stepwise manner to enable both graded and three-dimensional (3D) gene control in the yeast heat shock response. Molecular dissection revealed a condensate cascade. First, the transcription factor Hsf1 clusters upon partial dissociation from the chaperone Hsp70. Next, the coactivator Mediator partitions following further Hsp70 dissociation and Hsf1 phosphorylation. Finally, Pol II condenses, driving the emergent coalescence of HSR genes. Molecular analysis of a series of Hsf1 mutants revealed graded, rather than switch-like, transcriptional activity. Separation-of-function mutants showed that condensate formation can be decoupled from gene activation. Instead, fully assembled HSR condensates promote adaptive 3D genome reconfiguration, suggesting a role of transcriptional condensates beyond gene activation.

molecular biology↗

bioRxiv2021

Inducible transcriptional condensates drive 3D genome reorganization in the heat shock response

Mammalian developmental and disease-associated genes concentrate large quantities of the transcriptional machinery by forming membrane-less compartments known as transcriptional condensates. However, it is unknown whether these structures are evolutionarily conserved, capable of stress-inducible gene activation or involved in 3D genome reorganization. Here, we identify inducible transcriptional condensates in the yeast heat shock response (HSR). HSR condensates are biophysically dynamic spatiotemporal clusters of the sequence-specific transcription factor Heat shock factor 1 (Hsf1) with Mediator and RNA Pol II. Uniquely, HSR condensates drive the coalescence of multiple Hsf1 target genes, even those located on different chromosomes. Binding of the chaperone Hsp70 to a site on Hsf1 represses clustering, while an intrinsically disordered region on Hsf1 promotes condensate formation and intergenic interactions. Mutation of both Hsf1 determinants reprograms HSR condensates to become mammalian-like: constitutively active without intergenic coalescence. These results suggest that transcriptional condensates are ancient and flexible compartments of eukaryotic gene control.

molecular biology↗

bioRxiv2019

Maximizing the coding capacity of neuronal networks

Information in neuronal networks is encoded as spatiotemporal patterns of activity. The capacity of a network may thus be thought of as the number of stable spatiotemporal patterns it can generate. To understand what structural attributes of a network enable it to generate a profusion of stable patterns, we simulated an array of 9 x 9 neurons modelled as pulse-coupled oscillators. The structure of the network was inspired by the popular puzzle Sudoku such that its periodic responses mapped to solutions of the puzzle. Given that there are nearly a 109 possible Sudokus, this networks could possibly generate 109 spatiotemporal patterns. We show that the number of stable patterns were maximized when excitatory and inhibitory inputs to each neuron were balanced. When this balance was disrupted, only a subset of patterns with certain symmetries survived.

neuroscience↗

bioRxiv2018

Heat Shock Factor 1 Dynamically Restructures the Yeast Genome

Transcriptional induction of Heat Shock Protein (HSP) genes in yeast is accompanied by dynamic changes in their 3D structure and spatial organization, yet the molecular basis for these phenomena remains unknown. Using chromosome conformation capture and single cell imaging, we show that genes transcriptionally activated by Heat Shock Factor 1 (Hsf1) specifically interact across chromosomes and coalesce into diffraction-limited intranuclear foci. Genes activated by the alternative stress regulators Msn2 and Msn4, in contrast, do not interact among themselves nor with Hsf1 targets. Likewise, constitutively expressed genes, even those interposed between HSP genes, show no detectable interaction. Hsf1 forms discrete subnuclear puncta when stress-activated, and these puncta dissolve in concert with transcriptional attenuation, paralleling the kinetics of HSP gene coalescence and dissolution. Nuclear Hsf1 and RNA Pol II are both necessary for intergenic HSP gene interactions, while DNA-bound Hsf1 is necessary and sufficient to drive coalescence of a heterologous gene. Our findings demonstrate that Hsf1 can dynamically restructure the yeast genome.

genetics↗