Biomolecular condensates – extant relics or evolving microcompartments? DOI Creative Commons
Vijayaraghavan Rangachari

Communications Biology, Год журнала: 2023, Номер 6(1)

Опубликована: Июнь 21, 2023

Unprecedented discoveries during the past decade have unearthed ubiquitous presence of biomolecular condensates (BCs) in diverse organisms and their involvement a plethora biological functions. A predominant number BCs involve coacervation RNA proteins that demix from homogenous solutions by process phase separation well described liquid-liquid (LLPS), which results with higher concentration density bulk solution. provide simple effective means to achieve reversible spatiotemporal control cellular processes adaptation environmental stimuli an energy-independent manner. The journey into this phenomenon provides clues evolutionary origins life itself. Here I assemble some current historic on LLPS contemplate whether are extant hubs or evolving microcompartments. conclude biology could be as but co-evolving functionally compositionally complex microcompartments cells alongside membrane-bound organelles.

Язык: 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, Год журнала: 2022, Номер 136(3), С. 197 - 222

Опубликована: Фев. 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.

Язык: Английский

Процитировано

212

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

Reshma T Veettil,

Prashant Pradhan

и другие.

Cell, Год журнала: 2023, Номер 186(2), С. 327 - 345.e28

Опубликована: Янв. 1, 2023

Язык: Английский

Процитировано

189

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

и другие.

Molecular Cell, Год журнала: 2022, Номер 82(10), С. 1878 - 1893.e10

Опубликована: Май 1, 2022

Язык: Английский

Процитировано

168

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

Nucleus, Год журнала: 2022, Номер 13(1), С. 238 - 278

Опубликована: Ноя. 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.

Язык: Английский

Процитировано

73

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

Claudia Blaukopf,

Tracy Lou

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(18)

Опубликована: Апрель 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

Язык: Английский

Процитировано

50

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

Trends in Biochemical Sciences, Год журнала: 2023, Номер 48(5), С. 477 - 490

Опубликована: Фев. 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.

Язык: Английский

Процитировано

49

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

Nature, Год журнала: 2023, Номер 625(7993), С. 41 - 50

Опубликована: Дек. 13, 2023

Язык: Английский

Процитировано

45

Energy-driven genome regulation by ATP-dependent chromatin remodellers DOI
Sebastian Eustermann, Avinash B. Patel, Karl‐Peter Hopfner

и другие.

Nature Reviews Molecular Cell Biology, Год журнала: 2023, Номер 25(4), С. 309 - 332

Опубликована: Дек. 11, 2023

Язык: Английский

Процитировано

43

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

Martín Stortz,

Diego M. Presman, Valeria Levi

и другие.

Communications Biology, Год журнала: 2024, Номер 7(1)

Опубликована: Фев. 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.

Язык: Английский

Процитировано

26

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

и другие.

Molecular Systems Biology, Год журнала: 2021, Номер 17(9)

Опубликована: Сен. 1, 2021

Язык: Английский

Процитировано

64