Timed chromatin invasion during mitosis governs prototype foamy virus integration site selection and infectivity DOI Creative Commons
Floriane Lagadec, Pallavi Singh,

Christina Calmels

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 11, 2025

Abstract Selection of a suitable chromatin environment during retroviral integration is tightly regulated and multilayered process that involves interplay between viral host factors. However, whether intrinsic dynamics mitosis modulate genome invasion currently poorly described. Direct interaction the spumaretrovirus prototype foamy virus (PFV) Gag protein cellular has been described as major determinant for site selection. A previous chromatin-binding (CBS)–nucleosome co-crystal structure revealed an with histone H2A-H2B acidic patch via highly conserved arginine anchor residue. Yet, molecular mechanisms regulating Gag-chromatin capture PFV infection remain obscure. Here, we investigated kinetics interactions proviral PFV-infected synchronized cells. Using CBS variant viruses, showed alteration affinity nucleosome binding induced untimely tethering mitosis, decreased infectivity redistributed sites to markers associated late replication timing chromosomes. Mutant proteins were moreover defective in their ability displace H4 tail from condensed mitotic chromatin. These data indicate landscape Gag–nucleosome hosts selection determinants spumaretroviruses evolved high-affinity overcome early condensation optimal DNA tethering, infection.

Language: Английский

Spandrels of the cell nucleus DOI Creative Commons
Irina Solovei, Leonid A. Mirny

Current Opinion in Cell Biology, Journal Year: 2024, Volume and Issue: 90, P. 102421 - 102421

Published: Aug. 24, 2024

S.J. Gould and R. Lewontin in their famous "Spandrels paper" (1979) argued that many anatomical elements arise evolution not due to "current utility" but rather other "reasons for origin", such as developmental processes, physical constraints mechanical forces. Here, the same spirit, we argue a variety of molecular constraints, forces, alone or together, generate structures are detectable cell nucleus, yet these themselves may carry any specific function, being mere reflection processes produced them.

Language: Английский

Citations

5
Nucleolus and centromere Tyramide Signal Amplification-Seq reveals variable localization of heterochromatin in different cell types DOI Creative Commons
Pradeep Kumar, Omid Gholamalamdari, Yang Zhang

et al.

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: Sept. 13, 2024

Language: Английский

Citations

5
Two distinct chromatin modules regulate proinflammatory gene expression DOI Creative Commons
Isabelle Seufert, Irene Gerosa, Vassiliki Varamogianni‐Mamatsi

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 6, 2024

Abstract Various mechanisms have been proposed to explain gene activation and co-regulation, including enhancer-promoter interactions via chromatin looping the enrichment of transcription factors into hubs or condensates. However, these conclusions often stem from analyses individual loci, genome-wide studies exploring mechanistic differences with coupled expression are lacking. In this study, we dissected proinflammatory program induced by TNFα in primary human endothelial cells using NGS- imaging-based techniques. Our findings, enabled our novel RWireX approach for single-cell ATAC-seq analysis, revealed two distinct regulatory modules: autonomous links co-accessibility (ACs) between separated sites, domains contiguous (DCs) increased local factor binding. Genes ACs DCs exhibited different transcriptional bursting kinetics, highlighting existence structurally functionally modules response. These findings provide a framework understanding how achieve rapid precise control. Graphical abstract Highlights Two distinct, non-mutually exclusive modules, DCs, that regulate were identified based on deep scATAC-seq. represent long-range genomic regulation occurring more burst frequency. regions binding can modulate size. The AC/DC model integrates sequencing-based evidence microscopy observations hubs/condensates unified model.

Language: Английский

Citations

4
Timed chromatin invasion during mitosis governs prototype foamy virus integration site selection and infectivity DOI Creative Commons
Floriane Lagadec, Pallavi Singh,

Christina Calmels

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 11, 2025

Abstract Selection of a suitable chromatin environment during retroviral integration is tightly regulated and multilayered process that involves interplay between viral host factors. However, whether intrinsic dynamics mitosis modulate genome invasion currently poorly described. Direct interaction the spumaretrovirus prototype foamy virus (PFV) Gag protein cellular has been described as major determinant for site selection. A previous chromatin-binding (CBS)–nucleosome co-crystal structure revealed an with histone H2A-H2B acidic patch via highly conserved arginine anchor residue. Yet, molecular mechanisms regulating Gag-chromatin capture PFV infection remain obscure. Here, we investigated kinetics interactions proviral PFV-infected synchronized cells. Using CBS variant viruses, showed alteration affinity nucleosome binding induced untimely tethering mitosis, decreased infectivity redistributed sites to markers associated late replication timing chromosomes. Mutant proteins were moreover defective in their ability displace H4 tail from condensed mitotic chromatin. These data indicate landscape Gag–nucleosome hosts selection determinants spumaretroviruses evolved high-affinity overcome early condensation optimal DNA tethering, infection.

Language: Английский

Citations

0