The Essential Role of Architectural Noncoding RNA Neat1 in Cold-Induced Beige Adipocyte Differentiation in Mice DOI

Hikaru Toya,

Yuko Okamatsu‐Ogura, Saori Yokoi

et al.

RNA, Journal Year: 2024, Volume and Issue: 30(8), P. 1011 - 1024

Published: May 1, 2024

Neat1 is an architectural RNA that provides the structural basis for nuclear bodies known as paraspeckles. Although assembly processes by which organizes paraspeckle components are well-documented, physiological functions of not yet fully understood. This partly because knockout (KO) mice, lacking paraspeckles, do exhibit overt phenotypes under normal laboratory conditions. During our search conditions elicit clear in KO we discovered differentiation beige adipocytes—inducible thermogenic cells emerge upon cold exposure—is severely impaired these mutant mice. Neat1_2 , isoform transiently upregulated during early stages adipocyte differentiation, coinciding with increased formation. Genes altered expression typically cluster at specific chromosomal locations, some move closer to paraspeckles exposure. These observations suggest might coordinate regulation gene clusters controlling activity certain transcriptional condensates coregulate multiple genes. We propose findings highlight a potential role and modulating organization expression, potentially crucial adipocytes.

Language: Английский

Direct observation of a condensate effect on super-enhancer controlled gene bursting DOI Creative Commons
Manyu Du, Simon Hendrik Stitzinger, Jan-Hendrik Spille

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(2), P. 331 - 344.e17

Published: Jan. 1, 2024

Enhancers are distal DNA elements believed to loop and contact promoters control gene expression. Recently, we found diffraction-sized transcriptional condensates at genes controlled by clusters of enhancers (super-enhancers). However, a direct function endogenous in controlling expression remains elusive. Here, develop live-cell super-resolution multi-color 3D-imaging approaches investigate putative roles the regulation super-enhancer Sox2. In contrast enhancer distance, find instead that condensate's positional dynamics better predictor A basal bursting occurs when condensate is far (>1 μm), but burst size frequency enhanced moves proximity (<1 μm). Perturbations cohesin local do not prevent affect its enhancement. We propose three-way kissing model whereby interacts transiently with locus regulatory bursting.

Language: Английский

Citations

66
Transcriptional condensates: a blessing or a curse for gene regulation? DOI Creative Commons

Martín Stortz,

Diego M. Presman, Valeria Levi

et al.

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

Published: Feb. 16, 2024

Whether phase-separation is involved in the organization of transcriptional machinery and if it aids or inhibits process a matter intense debate. In this Mini Review, we will cover current knowledge regarding role condensates on gene expression regulation. We summarize latest discoveries relationship between condensate formation, genome organization, activity, focusing strengths weaknesses experimental approaches used to interrogate these aspects transcription living cells. Finally, discuss challenges for future research.

Language: Английский

Citations

26
Time will tell: comparing timescales to gain insight into transcriptional bursting DOI Creative Commons
Joseph V.W. Meeussen, Tineke L. Lenstra

Trends in Genetics, Journal Year: 2024, Volume and Issue: 40(2), P. 160 - 174

Published: Jan. 12, 2024

Recent imaging studies have captured the dynamics of regulatory events transcription inside living cells. These include factor (TF) DNA binding, chromatin remodeling and modification, enhancer-promoter (E-P) proximity, cluster formation, preinitiation complex (PIC) assembly. Together, these molecular culminate in stochastic bursts RNA synthesis, but their kinetic relationship remains largely unclear. In this review, we compare timescales upstream steps (input) with kinetics transcriptional bursting (output) to generate mechanistic models single We highlight open questions potential technical advances guide future endeavors toward a quantitative understanding regulation.

Language: Английский

Citations

24
Real-time single-molecule imaging of transcriptional regulatory networks in living cells DOI
Dong-Woo Hwang, Anna Maekiniemi, Robert H. Singer

et al.

Nature Reviews Genetics, Journal Year: 2024, Volume and Issue: 25(4), P. 272 - 285

Published: Jan. 9, 2024

Language: Английский

Citations

18
Transcription factor clusters as information transfer agents DOI Creative Commons
Rahul Munshi, Ling Jia, Sergey Ryabichko

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 1, 2025

Deciphering how genes interpret information from transcription factor (TF) concentrations within the cell nucleus remains a fundamental question in gene regulation. Recent advancements have revealed heterogeneous distribution of TF molecules, posing challenges to precisely decoding concentration signals. Using high-resolution single-cell imaging fluorescently tagged Bicoid living Drosophila embryos, we show that accumulation submicrometer clusters preserves spatial maternal gradient. These provide precise cues through intensity, size, and frequency. We further discover target colocalize with these an enhancer-binding affinity-dependent manner. Our modeling suggests clustering offers faster sensing mechanism for global nuclear than freely diffusing molecules detected by simple enhancers.

Language: Английский

Citations

4
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
Dynamic microenvironments shape nuclear organization and gene expression DOI Creative Commons
Gabriela Hayward-Lara, Matthew D. Fischer, Mustafa Mir

et al.

Current Opinion in Genetics & Development, Journal Year: 2024, Volume and Issue: 86, P. 102177 - 102177

Published: March 11, 2024

Language: Английский

Citations

11
Regulatory landscape of enhancer-mediated transcriptional activation DOI
Koji Kawasaki, Takashi Fukaya

Trends in Cell Biology, Journal Year: 2024, Volume and Issue: 34(10), P. 826 - 837

Published: Feb. 13, 2024

Language: Английский

Citations

9
Commonly asked questions about transcriptional activation domains DOI Creative Commons
Aditya Udupa,

Sanjana R. Kotha,

Max V. Staller

et al.

Current Opinion in Structural Biology, Journal Year: 2023, Volume and Issue: 84, P. 102732 - 102732

Published: Dec. 5, 2023

Eukaryotic transcription factors activate gene expression with their DNA-binding domains and activation domains. bind the genome by recognizing structurally related DNA sequences; they are structured, conserved, predictable from protein sequences. Activation recruit chromatin modifiers, coactivator complexes, or basal transcriptional machinery via diverse protein-protein interactions. have been called independent, modular units, but there many departures modularity, including interactions between these regions overlap in function. Compared to domains, poorly understood because intrinsically disordered, difficult predict This review, organized around commonly asked questions, describes recent progress that field has made understanding sequence features control predicting them sequence.

Language: Английский

Citations

13
Super-enhancer interactomes from single cells link clustering and transcription DOI Creative Commons

Derek J. Le,

Antonina Hafner, Sadhana Gaddam

et al.

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

Published: May 10, 2024

Summary Regulation of gene expression hinges on the interplay between enhancers and promoters, traditionally explored through pairwise analyses. Recent advancements in mapping genome folding, like GAM, SPRITE, multi-contact Hi-C, have uncovered multi-way interactions among super-enhancers (SEs), spanning megabases, yet not measured their frequency single cells or relationship clustering transcription. To close this gap, here we used multiplexed imaging to map 3D positions 376 SEs across thousands mammalian nuclei. Notably, our single-cell images reveal that while SE-SE contacts are rare, often form looser associations termed “communities”. These communities, averaging 4-5 SEs, assemble cooperatively under combined effects genomic tethers, Pol2 clustering, nuclear compartmentalization. Larger communities associated with more frequent larger transcriptional bursts. Our work provides insights about SE interactome challenge existing hypotheses context regulation.

Language: Английский

Citations

6