Reviewer #2 (Public Review): Dynamic modes of Notch transcription hubs conferring memory and stochastic activation revealed by live imaging the co-activator Mastermind DOI Open Access
F Javier deHaro-Arbona,

Charalambos Roussos,

Sarah Baloul

et al.

Published: Oct. 31, 2023

Developmental programming involves the accurate conversion of signaling levels and dynamics to transcriptional outputs. The relay in Notch pathway relies on nuclear complexes containing coactivator Mastermind (Mam). By tracking these real time, we reveal that they promote formation a dynamic transcription hub Notch-ON nuclei which concentrates key factors including Mediator CDK module. composition is labile persists after withdrawal conferring memory enables rapid reformation. Surprisingly, only third hubs progress state with nascent transcription, correlates Polymerase II core recruitment. probability increased by second signal. discovery target-gene probabilistic has far-reaching implications because it implies stochastic differences output can arise downstream receptor activation.

Language: Английский

Transcription regulation by biomolecular condensates DOI
Gaofeng Pei, Heankel Lyons, Pilong Li

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 8, 2024

Language: Английский

Citations

12
Feeling the force from within – new tools and insights into nuclear mechanotransduction DOI Creative Commons
Julien Morival,

Anna Hazelwood,

Jan Lammerding

et al.

Journal of Cell Science, Journal Year: 2025, Volume and Issue: 138(5)

Published: March 1, 2025

The ability of cells to sense and respond mechanical signals is essential for many biological processes that form the basis cell identity, tissue development maintenance. This process, known as mechanotransduction, involves crucial feedback between force biochemical signals, including epigenomic modifications establish transcriptional programs. These programs, in turn, reinforce properties its withstand perturbation. nucleus has long been hypothesized play a key role mechanotransduction due direct exposure forces transmitted through cytoskeleton, receiving cytoplasmic central function gene regulation. However, parsing out specific contributions from those surface cytoplasm remains substantial challenge. In this Review, we examine latest evidence on how regulates both via nuclear envelope (NE) epigenetic machinery elements within interior. We also explore establishing memory, characterized by mechanical, transcriptomic state persists after stimuli cease. Finally, discuss current challenges field present technological advances are poised overcome them.

Language: Английский

Citations

1
Mechanism of phase condensation for chromosome architecture and function DOI Creative Commons

J.-G. Park,

Jeong-Jun Kim, Je‐Kyung Ryu

et al.

Experimental & Molecular Medicine, Journal Year: 2024, Volume and Issue: 56(4), P. 809 - 819

Published: April 25, 2024

Abstract Chromosomal phase separation is involved in a broad spectrum of chromosome organization and functional processes. Nonetheless, the intricacy this process has left its molecular mechanism unclear. Here, we introduce principles governing connections to physiological roles context. Our primary focus contrasting two mechanisms: self-association-induced (SIPS) bridging-induced (BIPS). We provide comprehensive discussion distinct features characterizing these mechanisms offer illustrative examples that suggest their applicability. With detailed understanding mechanisms, explore associations with nucleosomes chromosomal biological functions. This review contributes exploration uncharted territory intricate interplay between architecture function.

Language: Английский

Citations

7
Plant RNA-binding proteins: Phase separation dynamics and functional mechanisms underlying plant development and stress responses DOI Creative Commons

Sheng Fan,

Yu Zhang,

Shaobo Zhu

et al.

Molecular Plant, Journal Year: 2024, Volume and Issue: 17(4), P. 531 - 551

Published: Feb. 27, 2024

RNA-binding proteins (RBPs) accompany RNA from synthesis to decay, mediating every aspect of metabolism and impacting diverse cellular developmental processes in eukaryotes. Many RBPs undergo phase separation along with their bound form function dynamic membraneless biomolecular condensates for spatiotemporal coordination or regulation metabolism. Increasing evidence suggests that phase-separating domains intrinsically disordered regions play important roles plant development stress adaptation. Here, we summarize the current knowledge about how partitioning into controls enables sensing experimental changes confer growth plasticity under conditions, a focus on dynamics functional mechanisms RBP-rich nuclear cytoplasmic granules We also discuss multiple factors, such as environmental signals, protein modifications, N

Language: Английский

Citations

6
Redox regulation of gene expression: proteomics reveals multiple previously undescribed redox-sensitive cysteines in transcription complexes and chromatin modifiers DOI
Avilien Dard, Frank Van Breusegem, Amna Mhamdi

et al.

Journal of Experimental Botany, Journal Year: 2024, Volume and Issue: 75(15), P. 4476 - 4493

Published: April 20, 2024

Redox signalling is crucial for regulating plant development and adaptation to environmental changes. Proteins with redox-sensitive cysteines can sense oxidative stress modulate their functions. Recent proteomics efforts have comprehensively mapped the proteins targeted by modifications. The nucleus, epicentre of transcriptional reprogramming, contains a large number that control gene expression. Specific transcription factors long been recognized as key players in decoding redox signals nucleus thus responses. Consequently, regulation nuclear machinery its cofactors has received less attention. In this review, we screened proteomic datasets on core complexes chromatin modifiers Arabidopsis thaliana. Our analysis indicates affects every step transcription, from initiation elongation termination. We report previously undescribed subunits discuss emerging challenges unravelling landscape redox-regulated processes involved transcription.

Language: Английский

Citations

6
Nuclear basket proteins Mlp1 and Nup2 drive heat shock-induced 3D genome restructuring DOI Creative Commons
Suman Mohajan, Linda S Rubio, David S. Gross

et al.

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

Published: Jan. 2, 2025

ABSTRACT The nuclear pore complex (NPC), a multisubunit located within the envelope, regulates RNA export and import of proteins. Here we address role NPC in driving thermal stress-induced 3D genome repositioning Heat Shock Responsive ( HSR ) genes yeast. We found that two basket proteins, Mlp1 Nup2, although dispensable for integrity, are required into coalesced chromatin clusters, consistent with their strong, heat shock-dependent recruitment to gene regulatory coding regions. clustering occurs predominantly nucleoplasm is independent essential scaffold-associated proteins Nup1 Nup145. Notably, double depletion Nup2 has little effect on formation Factor 1 (Hsf1)-containing transcriptional condensates, Hsf1 Pol II genes, or mRNA abundance. Our results define restructuring extrinsic downstream activation.

Language: Английский

Citations

0
Nuclear Basket Proteins Mlp1 and Nup2 Drive Heat Shock–Induced 3D Genome Restructuring DOI Creative Commons
Suman Mohajan, Linda S Rubio, David S. Gross

et al.

Published: Jan. 31, 2025

The nuclear pore complex (NPC), a multisubunit located within the envelope, regulates RNA export and import of proteins. Here we address role NPC in driving thermal stress-induced 3D genome repositioning _Heat Shock Responsive_ (_HSR_) genes yeast. We found that two basket proteins, Mlp1 Nup2, although dispensable for integrity, are required _HSR_ into coalesced chromatin clusters, consistent with their strong, heat shock-dependent recruitment to gene regulatory coding regions. clustering occurs predominantly nucleoplasm is independent essential scaffold-associated proteins Nup1 Nup145. Notably, double depletion Nup2 has little effect on formation Heat Factor 1 (Hsf1)-containing transcriptional condensates, Hsf1 Pol II genes, or mRNA abundance. Our results define restructuring extrinsic downstream activation.

Language: Английский

Citations

0
Transcription‐coupled repair: tangled up in convoluted repair DOI Creative Commons
Diana A. Llerena Schiffmacher, Yun Jin Pai, Alex Pines

et al.

FEBS Journal, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

Significant progress has been made in understanding the mechanism of transcription‐coupled nucleotide excision repair (TC‐NER); however, numerous aspects remain elusive, including TC‐NER regulation, lesion‐specific and cell type‐specific complex composition, structural insights, lesion removal dynamics living cells. This review summarizes discusses recent advancements TC‐NER, focusing on newly identified interactors, mechanistic insights from cryo‐electron microscopy (Cryo‐EM) studies live imaging, contribution post‐translational modifications (PTMs), such as ubiquitin, regulating TC‐NER. Furthermore, we elaborate consequences deficiencies address role accumulated damage persistent lesion‐stalled RNA polymerase II (Pol II) major drivers disease phenotype Cockayne syndrome (CS) its related disorders. In this context, also discuss severe effects transcription‐blocking lesions (TBLs) neurons, highlighting their susceptibility to damage. Lastly, explore potential investigating three‐dimensional (3D) chromatin structure phase separation uncover further into essential DNA pathway.

Language: Английский

Citations

0
Selective phase separation of transcription factors is driven by orthogonal molecular grammar DOI Creative Commons
Mark D. Driver, Patrick R. Onck

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 31, 2025

Protein production is critically dependent on gene transcription rates, which are regulated by RNA polymerase and a large collection of different factors (TFs). How these selectively address genes only partially known. Recent discoveries show that the differential condensation separate TF families through phase separation may contribute to selectivity. Here we this conducting studies six TFs from three with residue-scale coarse-grained molecular dynamics simulations. Our exploration ternary diagrams reveals four dominant sticker motifs two orthogonal driving forces dictate resultant condensate morphology, pointing sequence-dependent grammar as generic mechanism drives selective transcriptional in expression. Transcription factor (TF) rates. Exploration morphology.

Language: Английский

Citations

0
RNA polymerase II partitioning is a shared feature of diverse oncofusion condensates DOI
Heankel Lyons, Prashant Pradhan, Gopinath Prakasam

et al.

Cell, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0