Dynamic Opposition of Histone Modifications DOI
Ana María Garzón Porras, Emma J. Chory, Berkley E. Gryder

et al.

ACS Chemical Biology, Journal Year: 2022, Volume and Issue: 18(4), P. 1027 - 1036

Published: March 17, 2022

Gene transcription does not only require writers of active histone modifications; on-site opposition by erasers is essential for many genes. Here, we propose the concept dynamic modifications to explain this conundrum. We highlight requirement HDACs acetylation balance at superenhancers, and KDM5A H4K3me3 recycling highly gene promoters. that post-translational regulate charge biomolecular condensate formation nucleosome turnover form a short-term memory informs lock-and-step checkpoints chromatin engagement RNA polymerase II.

Language: Английский

The Mediator complex as a master regulator of transcription by RNA polymerase II DOI Open Access
William F. Richter, Shraddha Nayak, Janet Iwasa

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 23(11), P. 732 - 749

Published: June 20, 2022

Language: Английский

Citations

198

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

Condensate interfacial forces reposition DNA loci and probe chromatin viscoelasticity DOI Creative Commons
Amy R. Strom, Yoonji Kim, Hongbo Zhao

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(19), P. 5282 - 5297.e20

Published: Aug. 20, 2024

Biomolecular condensates assemble in living cells through phase separation and related transitions. An underappreciated feature of these dynamic molecular assemblies is that they form interfaces with other cellular structures, including membranes, cytoskeleton, DNA RNA, membraneless compartments. These are expected to give rise capillary forces, but there few ways quantifying harnessing forces cells. Here, we introduce viscoelastic chromatin tethering organization (VECTOR), which uses light-inducible biomolecular generate at targeted loci. VECTOR can be utilized programmably reposition genomic loci on a timescale seconds minutes, quantitatively revealing local heterogeneity the material properties chromatin. synthetic built from components naturally liquid-like structures cells, highlighting potential role for native do work reorganize genome impact architecture.

Language: Английский

Citations

27

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

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

Disordered C-terminal domain drives spatiotemporal confinement of RNAPII to enhance search for chromatin targets DOI
Yick Hin Ling, Ziyang Ye,

Chloe Liang

et al.

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(4), P. 581 - 592

Published: March 28, 2024

Language: Английский

Citations

9

Real-time visualization of reconstituted transcription reveals RNA polymerase II activation mechanisms at single promoters DOI Creative Commons
Megan Palacio, Dylan J. Taatjes

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

Published: Jan. 6, 2025

RNA polymerase II (RNAPII) is regulated by sequence-specific transcription factors (TFs) and the pre-initiation complex (PIC): TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIH, Mediator. TFs Mediator contain intrinsically-disordered regions (IDRs) form phase-separated condensates, but how IDRs control RNAPII function remains poorly understood. Using purified PIC factors, we developed a Real-time In-vitro Fluorescence Transcription assay (RIFT) for second-by-second visualization of at hundreds promoters simultaneously. We show rapid activation IDR-dependent, without condensate formation. For example, MED1-IDR can functionally replace native TF, activating with similar (not identical) kinetics; however, squelches as condensate, activates single-protein. cooperatively activate bursting re-initiation surprisingly, drive TF-promoter recruitment, TF-DNA binding. Collectively, RIFT addressed questions largely intractable cell-based methods, yielding mechanistic insights about IDRs, enhancer-promoter communication, that complement live-cell imaging data.

Language: Английский

Citations

1

Aberrant liquid-liquid phase separation and amyloid aggregation of proteins related to neurodegenerative diseases DOI

Azeem Ahmad,

Vladimir N. Uversky, Rizwan Hasan Khan

et al.

International Journal of Biological Macromolecules, Journal Year: 2022, Volume and Issue: 220, P. 703 - 720

Published: Aug. 23, 2022

Language: Английский

Citations

36

Functional organization of RNA polymerase II in nuclear subcompartments DOI
Karsten Rippe, Argyris Papantonis

Current Opinion in Cell Biology, Journal Year: 2022, Volume and Issue: 74, P. 88 - 96

Published: Feb. 1, 2022

Language: Английский

Citations

34

Mechanisms and Functions of the RNA Polymerase II General Transcription Machinery during the Transcription Cycle DOI Creative Commons
Stephen R. Archuleta, James A. Goodrich, Jennifer F. Kugel

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(2), P. 176 - 176

Published: Feb. 1, 2024

Central to the development and survival of all organisms is regulation gene expression, which begins with process transcription catalyzed by RNA polymerases. During protein-coding genes, general factors (GTFs) work alongside polymerase II (Pol II) assemble preinitiation complex at start site, open promoter DNA, initiate synthesis nascent messenger RNA, transition productive elongation, ultimately terminate transcription. Through these different stages transcription, Pol dynamically phosphorylated C-terminal tail its largest subunit, serving as a control mechanism for elongation signaling/binding platform co-transcriptional factors. The large number core protein participating in fundamental steps add dense layers that contribute complexity temporal spatial expression within any given cell type. system highly conserved across levels eukaryotes; however, most information here will focus on human system. This review walks through various from assembly termination, highlighting functions mechanisms machinery participates each stage.

Language: Английский

Citations

8