SGF29 nuclear condensates reinforce cellular aging DOI Creative Commons
Kaowen Yan, Qianzhao Ji, Dongxin Zhao

et al.

Cell Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Nov. 7, 2023

Phase separation, a biophysical segregation of subcellular milieus referred as condensates, is known to regulate transcription, but its impacts on physiological processes are less clear. Here, we demonstrate the formation liquid-like nuclear condensates by SGF29, component SAGA transcriptional coactivator complex, during cellular senescence in human mesenchymal progenitor cells (hMPCs) and fibroblasts. The Arg 207 within intrinsically disordered region identified key amino acid residue for SGF29 form phase separation. Through epigenomic transcriptomic analysis, our data indicated that both condensate H3K4me3 binding essential establishing precise chromatin location, recruiting factors co-activators target specific genomic loci, initiating expression genes associated with senescence, such CDKN1A. alone, however, may not be sufficient drive or achieve transactivation functions. Our study establishes link between separation aging regulation, highlighting functional unit facilitate shaping landscapes aging.

Language: Английский

The Hippo pathway in cancer: YAP/TAZ and TEAD as therapeutic targets in cancer DOI Creative Commons
Richard Cunningham, Carsten Gram Hansen

Clinical Science, Journal Year: 2022, Volume and Issue: 136(3), P. 197 - 222

Published: Feb. 1, 2022

Abstract Tumorigenesis is a highly complex process, involving many interrelated and cross-acting signalling pathways. One such pathway that has garnered much attention in the field of cancer research over last decade Hippo pathway. Consisting two antagonistic modules, plays an integral role both tumour suppressive oncogenic processes, generally via regulation diverse set genes involved range biological functions. This review discusses history within context explores some most recent discoveries as to how this critical transducer cellular can influence progression. A special focus on various efforts therapeutically target key effectors preclinical clinical settings.

Language: Английский

Citations

208

Functional partitioning of transcriptional regulators by patterned charge blocks DOI Creative Commons
Heankel Lyons,

Reshma T Veettil,

Prashant Pradhan

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(2), P. 327 - 345.e28

Published: Jan. 1, 2023

Language: Английский

Citations

189

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

Chromatin accessibility: methods, mechanisms, and biological insights DOI Creative Commons
Andrés Mansisidor, Viviana I. Risca

Nucleus, Journal Year: 2022, Volume and Issue: 13(1), P. 238 - 278

Published: Nov. 20, 2022

Access to DNA is a prerequisite the execution of essential cellular processes that include transcription, replication, chromosomal segregation, and repair. How proteins regulate these function in context chromatin its dynamic architectures an intensive field study. Over past decade, genome-wide assays new imaging approaches have enabled greater understanding how access genome regulated by nucleosomes associated proteins. Additional mechanisms may control accessibility vivo compaction phase separation – are beginning be understood. Here, we review ongoing development measurements, summarize different molecular structural shape landscape, detail many important biological functions linked accessibility.

Language: Английский

Citations

73

In diverse conditions, intrinsic chromatin condensates have liquid-like material properties DOI Creative Commons
Bryan A. Gibson,

Claudia Blaukopf,

Tracy Lou

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(18)

Published: April 24, 2023

Nuclear DNA in eukaryotes is wrapped around histone proteins to form nucleosomes on a chromatin fiber. Dynamic folding of the fiber into loops and variations degree compaction regulate essential processes such as transcription, recombination, mitotic chromosome segregation. Our understanding physical properties that allow be dynamically remodeled even highly compacted states limited. Previously, we reported has an intrinsic capacity phase separate dynamic liquid-like condensates, which can regulated by cellular factors [B. A. Gibson et al. , Cell 179 470–484.e421 (2019)]. Recent contradictory reports claim specific set solution conditions required for fluidity condensates would otherwise solid [J. C. Hansen, K. Maeshima, M. J. Hendzel, Epigenetics Chromatin 14 50 (2021); H. Strickfaden 183 1772–1784.e1713 (2020)]. We sought resolve these discrepancies, our ability translate with confidence biophysical observations cells requires their precise characterization. Moreover, whether assemblies are or static affects how loop extrusion, remodeling will engage them inside cells. Here, show diverse without buffering components fragments separated fluids vitro. also explore sample preparation imaging affect experimental observation condensate dynamics. Last, describe vitro behaviors locally but globally constrained movement observed

Language: Английский

Citations

50

Interaction modules that impart specificity to disordered protein DOI Creative Commons
Kateřina Čermáková, H. Courtney Hodges

Trends in Biochemical Sciences, Journal Year: 2023, Volume and Issue: 48(5), P. 477 - 490

Published: Feb. 6, 2023

Intrinsically disordered regions (IDRs) are especially enriched among proteins that regulate chromatin and transcription. As a result, mechanisms influence specificity of IDR-driven interactions have emerged as exciting unresolved issues for understanding gene regulation. We review the molecular elements frequently found within IDRs confer regulatory specificity. In particular, we summarize differing roles low-complexity (LCRs) short linear motifs (SLiMs) towards selective nuclear Examination highlights SLiMs organizers selectivity, with widespread in regulation integration cellular signals. Analysis recurrent between folded domains suggests diverse avenues to phase-separated condensates opportunities manipulate these control biological activity.

Language: Английский

Citations

49

Hold out the genome: a roadmap to solving the cis-regulatory code DOI
Carl G. de Boer, Jussi Taipale

Nature, Journal Year: 2023, Volume and Issue: 625(7993), P. 41 - 50

Published: Dec. 13, 2023

Language: Английский

Citations

45

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

RNA polymerase II clusters form in line with surface condensation on regulatory chromatin DOI
Agnieszka Pancholi, Tim Klingberg, Weichun Zhang

et al.

Molecular Systems Biology, Journal Year: 2021, Volume and Issue: 17(9)

Published: Sept. 1, 2021

Language: Английский

Citations

64

Physical Nature of Chromatin in the Nucleus DOI Open Access
Kazuhiro Maeshima, Shiori Iida, Sachiko Tamura

et al.

Cold Spring Harbor Perspectives in Biology, Journal Year: 2021, Volume and Issue: 13(5), P. a040675 - a040675

Published: April 5, 2021

Kazuhiro Maeshima1,2, Shiori Iida1,2 and Sachiko Tamura1 1Genome Dynamics Laboratory, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan 2Department School Life Science, Sokendai (Graduate University for Advanced Studies), Correspondence: kmaeshim{at}nig.ac.jp

Language: Английский

Citations

62