A Stochastic Model of Gene Expression with Polymerase Recruitment and Pause Release DOI Creative Commons
Zhixing Cao, Т. С. Филатова, Diego A. Oyarzún

et al.

Biophysical Journal, Journal Year: 2020, Volume and Issue: 119(5), P. 1002 - 1014

Published: Aug. 3, 2020

Language: Английский

RNA-Mediated Feedback Control of Transcriptional Condensates DOI Creative Commons
Jonathan E. Henninger, Ozgur Oksuz, Krishna Shrinivas

et al.

Cell, Journal Year: 2020, Volume and Issue: 184(1), P. 207 - 225.e24

Published: Dec. 16, 2020

Language: Английский

Citations

454

Mechanisms of enhancer action: the known and the unknown DOI Creative Commons

Anil K. Panigrahi,

Bert W. O’Malley

Genome biology, Journal Year: 2021, Volume and Issue: 22(1)

Published: April 15, 2021

Abstract Differential gene expression mechanisms ensure cellular differentiation and plasticity to shape ontogenetic phylogenetic diversity of cell types. A key regulator differential programs are the enhancers, gene-distal cis -regulatory sequences that govern spatiotemporal quantitative dynamics target genes. Enhancers widely believed physically contact promoters effect transcriptional activation. However, our understanding full complement regulatory proteins definitive mechanics enhancer action is incomplete. Here, we review recent findings present some emerging concepts on also outline a set outstanding questions.

Language: Английский

Citations

267

The epigenetic basis of cellular heterogeneity DOI
Benjamin C. Carter, Keji Zhao

Nature Reviews Genetics, Journal Year: 2020, Volume and Issue: 22(4), P. 235 - 250

Published: Nov. 26, 2020

Language: Английский

Citations

239

Enhancer-promoter communication: hubs or loops? DOI
Bomyi Lim, Michael Levine

Current Opinion in Genetics & Development, Journal Year: 2020, Volume and Issue: 67, P. 5 - 9

Published: Nov. 14, 2020

Language: Английский

Citations

146

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

Mechanical Regulation of Transcription: Recent Advances DOI Creative Commons
Kaustubh Wagh,

Momoko Ishikawa,

David A. Garcia

et al.

Trends in Cell Biology, Journal Year: 2021, Volume and Issue: 31(6), P. 457 - 472

Published: March 10, 2021

Mechanotransduction is the ability of a cell to sense mechanical cues from its microenvironment and convert them into biochemical signals elicit adaptive transcriptional other cellular responses. Here, we describe recent advances in field regulation transcription, highlight epigenome as key novel aspect mechanotransduction, technological that could further elucidate link between stimuli gene expression. In this review, emphasize importance mechanotransduction one governing principles cancer progression, underscoring need conduct studies molecular mechanisms involved sensing coordinating

Language: Английский

Citations

104

Phase separation in genome organization across evolution DOI Creative Commons
Marina Feric,

Tom Misteli

Trends in Cell Biology, Journal Year: 2021, Volume and Issue: 31(8), P. 671 - 685

Published: March 23, 2021

Language: Английский

Citations

74

Systematic comparison of high-throughput single-cell RNA-seq methods for immune cell profiling DOI Creative Commons
Tracy Yamawaki,

Daniel Lu,

Daniel C. Ellwanger

et al.

BMC Genomics, Journal Year: 2021, Volume and Issue: 22(1)

Published: Jan. 20, 2021

Abstract Background Elucidation of immune populations with single-cell RNA-seq has greatly benefited the field immunology by deepening characterization heterogeneity and leading to discovery new subtypes. However, methods inherently suffer from limitations in recovery complete transcriptomes due prevalence cellular transcriptional dropout events. This issue is often compounded limited sample availability prior knowledge heterogeneity, which can confound data interpretation. Results Here, we systematically benchmarked seven high-throughput methods. We prepared 21 libraries under identical conditions a defined mixture two human murine lymphocyte cell lines, simulating across immune-cell types sizes. evaluated their rate, library efficiency, sensitivity, ability recover expression signatures for each type. observed higher mRNA detection sensitivity 10x Genomics 5′ v1 3′ v3 demonstrate that these have fewer events, facilitates identification differentially-expressed genes improves concordance profiles bulk signatures. Conclusion Overall, our mixtures provides useful metrics, guide selection method profiling more complex usually found vivo.

Language: Английский

Citations

67

Quantitative imaging of transcription in living Drosophila embryos reveals the impact of core promoter motifs on promoter state dynamics DOI Creative Commons
Virginia L Pimmett, Matthieu Dejean, Carola Fernandez

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: July 23, 2021

Abstract Genes are expressed in stochastic transcriptional bursts linked to alternating active and inactive promoter states. A major challenge transcription is understanding how composition dictates bursting, particularly multicellular organisms. We investigate two key Drosophila developmental motifs, the TATA box (TATA) Initiator (INR). Using live imaging embryos new computational methods, we demonstrate that bursting occurs on multiple timescales ranging from seconds minutes. TATA-containing promoters INR-containing exhibit distinct dynamics, with one or separate rate-limiting steps respectively. associated long states, high rates of polymerase initiation, short-lived, infrequent In contrast, INR motif leads which relates promoter-proximal pausing. Surprisingly, model suggests pausing not obligatory, but stochastically for a subset polymerases. Overall, our results provide rationale switching during zygotic genome activation.

Language: Английский

Citations

63