Transcription regulates the spatio-temporal dynamics of genes through micro-compartmentalization DOI Creative Commons

Hossein Salari,

Geneviève Fourel,

Daniel Jost

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 19, 2023

Abstract Although our understanding of the involvement heterochromatin architectural factors in shaping nuclear organization is improving, there still ongoing debate regarding role active genes this process. In study, we utilize publicly-available Micro-C data from mouse embryonic stem cells to investigate relationship between gene transcription and 3D folding. Our analysis uncovers a nonmonotonic - globally positive correlation intragenic contact density Pol II occupancy, independent cohesin-based loop extrusion. Through development biophysical model integrating dynamics within polymer chromosome organization, demonstrate that II-mediated attractive interactions with limited valency transcribed regions yield quantitative predictions consistent chromosome-conformation-capture live-imaging experiments. work provides compelling evidence transcriptional activity shapes 4D genome through micro-compartmentalization.

Language: Английский

Transcription activation is enhanced by multivalent interactions independent of phase separation DOI Creative Commons
Jorge Trojanowski, Lukas Frank, Anne Rademacher

et al.

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(10), P. 1878 - 1893.e10

Published: May 1, 2022

Language: Английский

Citations

168
Region Capture Micro-C reveals coalescence of enhancers and promoters into nested microcompartments DOI
Viraat Y. Goel, Miles K. Huseyin, Anders S. Hansen

et al.

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(6), P. 1048 - 1056

Published: May 8, 2023

Language: Английский

Citations

129
RNA granules: functional compartments or incidental condensates? DOI Open Access
Andrea Putnam, Laura Thomas, Géraldine Seydoux

et al.

Genes & Development, Journal Year: 2023, Volume and Issue: 37(9-10), P. 354 - 376

Published: May 1, 2023

RNA granules are mesoscale assemblies that form in the absence of limiting membranes. contain factors for biogenesis and turnover often assumed to represent specialized compartments biochemistry. Recent evidence suggests assemble by phase separation subsoluble ribonucleoprotein (RNP) complexes partially demix from cytoplasm or nucleoplasm. We explore possibility some nonessential condensation by-products arise when RNP exceed their solubility limit as a consequence cellular activity, stress, aging. describe use evolutionary mutational analyses single-molecule techniques distinguish functional "incidental condensates."

Language: Английский

Citations

57
Formin-mediated nuclear actin at androgen receptors promotes transcription DOI
Julian Knerr, Ralf Werner, Carsten Schwan

et al.

Nature, Journal Year: 2023, Volume and Issue: 617(7961), P. 616 - 622

Published: March 27, 2023

Language: Английский

Citations

36
Orphan quality control shapes network dynamics and gene expression DOI Creative Commons
Kevin G. Mark,

SriDurgaDevi Kolla,

Jacob D. Aguirre

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(16), P. 3460 - 3475.e23

Published: July 20, 2023

All eukaryotes require intricate protein networks to translate developmental signals into accurate cell fate decisions. Mutations that disturb interactions between network components often result in disease, but how the composition and dynamics of complex are established remains poorly understood. Here, we identify E3 ligase UBR5 as a signaling hub helps degrade unpaired subunits multiple transcriptional regulators act within centered on c-Myc oncoprotein. Biochemical structural analyses show binds motifs only become available upon dissociation. By rapidly turning over transcription factor subunits, establishes dynamic allow cells effectively execute gene expression while remaining receptive environmental signals. We conclude orphan quality control plays an essential role establishing networks, which may explain conserved need for degradation during offers opportunities modulate disease.

Language: Английский

Citations

36
Transcription regulates the spatio-temporal dynamics of genes through micro-compartmentalization DOI Creative Commons

Hossein Salari,

Geneviève Fourel,

Daniel Jost

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 25, 2024

Abstract Although our understanding of the involvement heterochromatin architectural factors in shaping nuclear organization is improving, there still ongoing debate regarding role active genes this process. In study, we utilize publicly-available Micro-C data from mouse embryonic stem cells to investigate relationship between gene transcription and 3D folding. Our analysis uncovers a nonmonotonic - globally positive correlation intragenic contact density Pol II occupancy, independent cohesin-based loop extrusion. Through development biophysical model integrating dynamics within polymer chromosome organization, demonstrate that II-mediated attractive interactions with limited valency transcribed regions yield quantitative predictions consistent chromosome-conformation-capture live-imaging experiments. work provides compelling evidence transcriptional activity shapes 4D genome through micro-compartmentalization.

Language: Английский

Citations

10
Nuclear actin dynamics and functions at a glance DOI
Svenja Ulferts, Massimo Lopes, Kei Miyamoto

et al.

Journal of Cell Science, Journal Year: 2024, Volume and Issue: 137(6)

Published: March 15, 2024

Actin is well known for its cytoskeletal functions, where it helps to control and maintain cell shape architecture, as regulating migration intracellular cargo transport, among others. However, actin also prevalent in the nucleus, genome-regulating roles have been described, including being part of chromatin-remodeling complexes. More recently, with help advances microscopy techniques specialized imaging probes, direct visualization nuclear filament dynamics has helped elucidate new actin, such cycle regulation, DNA replication repair, chromatin organization transcriptional condensate formation. In this Cell Science at a Glance article, we summarize signaling events driving dynamic assembly into filaments various structures within compartment essential genome functions. Additionally, highlight physiological role F-actin meiosis early embryonic development.

Language: Английский

Citations

9
Region Capture Micro-C reveals coalescence of enhancers and promoters into nested microcompartments DOI Creative Commons
Viraat Y. Goel, Miles K. Huseyin, Anders S. Hansen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: July 14, 2022

Although enhancers are central to the regulation of mammalian gene expression, mechanisms underlying Enhancer-Promoter (E-P) interactions remain unclear. Chromosome conformation capture (3C) methods effectively large-scale 3D genome structure but struggle achieve depth necessary resolve fine-scale E-P interactions. Here, we develop Region Capture Micro-C (RCMC) by combining MNase-based 3C with a tiling region-capture approach and generate deepest maps reported thus far only modest sequencing. By applying RCMC in mouse embryonic stem cells reaching genome-wide equivalent ∼200 billion unique contacts, reveals previously unresolvable patterns highly nested focal interactions, which term microcompartments. Microcompartments frequently connect promoters largely robust loss loop extrusion inhibition transcription. We therefore propose that many form through compartmentalization mechanism, may explain why acute cohesin depletion modestly affects global expression.

Language: Английский

Citations

35
SUN2 mediates calcium-triggered nuclear actin polymerization to cluster active RNA polymerase II DOI Creative Commons
Svenja Ulferts, Robert Grosse

EMBO Reports, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 24, 2024

Abstract The nucleoskeleton is essential for nuclear architecture as well genome integrity and gene expression. In addition to lamins, titin or spectrins, dynamic actin filament polymerization has emerged a potential intranuclear structural element but its functions are less explored. Here we found that calcium elevations trigger rapid assembly requiring the membrane protein SUN2 independently of function component LINC complex. Instead, colocalized associated with formin nucleator INF2 in envelope calcium-regulated manner. Moreover, required active RNA polymerase II (RNA Pol II) clustering response elevations. Thus, our data uncover SUN2-formin module linking promote signal-dependent spatial reorganization II.

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