The Arthropoda-specific Tramtrack group BTB protein domains use previously unknown interface to form hexamers DOI Creative Commons
Artem Bonchuk, Konstantin Balagurov, Rozbeh Baradaran

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Sept. 2, 2024

BTB (bric-a-brack, Tramtrack, and broad complex) is a diverse group of protein-protein interaction domains found within metazoan proteins. Transcription factors contain dimerizing subtype with characteristic N-terminal extension. The Tramtrack (TTK) distinct type domain, which can multimerize. Single-particle cryo-EM microscopy revealed that the TTK-type assemble into hexameric structure consisting three canonical dimers connected through previously uncharacterized interface. We demonstrated are only in Arthropods have undergone lineage-specific expansion modern insects. Drosophila genome encodes 24 transcription domains, whereas four non-TTK-type domains. Yeast two-hybrid analysis an unusually potential for heteromeric associations presumably dimer-dimer Thus, structurally functionally protein specific to Arthropodan factors.

Language: Английский

Chromosome-level organization of the regulatory genome in the Drosophila nervous system DOI Creative Commons
Giriram Mohana, Julien Dorier, Xiao Li

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(18), P. 3826 - 3844.e26

Published: Aug. 1, 2023

Language: Английский

Citations

51

GAGA-associated factor fosters loop formation in the Drosophila genome DOI Creative Commons
Xiao Li, Xiaona Tang, Xinyang Bing

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(9), P. 1519 - 1526.e4

Published: March 31, 2023

Language: Английский

Citations

47

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

A pioneer factor locally opens compacted chromatin to enable targeted ATP-dependent nucleosome remodeling DOI
Megan A. Frederick, Kaylyn E. Williamson, Meilín Fernández García

et al.

Nature Structural & Molecular Biology, Journal Year: 2022, Volume and Issue: 30(1), P. 31 - 37

Published: Dec. 19, 2022

Language: Английский

Citations

46

The control of transcriptional memory by stable mitotic bookmarking DOI Creative Commons
Maëlle Bellec, Jérémy Dufourt, George Hunt

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: March 4, 2022

Abstract To maintain cellular identities during development, gene expression profiles must be faithfully propagated through cell generations. The reestablishment of patterns upon mitotic exit is mediated, in part, by transcription factors (TF) bookmarking. However, the mechanisms and functions TF bookmarking early embryogenesis remain poorly understood. In this study, taking advantage naturally synchronized mitoses Drosophila embryos, we provide evidence that GAGA pioneer factor (GAF) acts as a stable bookmarker zygotic genome activation. We show that, mitosis, GAF remains associated to large fraction its interphase targets, including at cis -regulatory sequences key developmental genes with both active repressive chromatin signatures. targets are globally accessible mitosis bookmarked via histone acetylation (H4K8ac). By monitoring kinetics transcriptional activation living report binding establishes competence for rapid exit.

Language: Английский

Citations

39

Chromatin accessibility in the Drosophila embryo is determined by transcription factor pioneering and enhancer activation DOI Creative Commons
Kaelan Brennan, Melanie Weilert, Sabrina Krueger

et al.

Developmental Cell, Journal Year: 2023, Volume and Issue: 58(19), P. 1898 - 1916.e9

Published: Aug. 8, 2023

Chromatin accessibility is integral to the process by which transcription factors (TFs) read out cis-regulatory DNA sequences, but it difficult differentiate between TFs that drive and those do not. Deep learning models learn complex sequence rules provide an unprecedented opportunity dissect this problem. Using zygotic genome activation in Drosophila as a model, we analyzed high-resolution TF binding chromatin data with interpretable deep performed genetic validation experiments. We identify hierarchical relationship pioneer Zelda involved axis patterning. consistently pioneers proportional motif affinity, whereas patterning augment contexts where they mediate enhancer activation. conclude occurs two tiers: one through pioneering, makes enhancers accessible not necessarily active, second when correct combination of leads

Language: Английский

Citations

37

Pioneer factors: roles and their regulation in development DOI Creative Commons
Amandine Barral, Kenneth S. Zaret

Trends in Genetics, Journal Year: 2023, Volume and Issue: 40(2), P. 134 - 148

Published: Nov. 7, 2023

Language: Английский

Citations

36

Transcription Factor Dynamics: One Molecule at a Time DOI Creative Commons
Kaustubh Wagh, Diana A. Stavreva, Arpita Upadhyaya

et al.

Annual Review of Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 39(1), P. 277 - 305

Published: Aug. 4, 2023

Cells must tightly regulate their gene expression programs and yet rapidly respond to acute biochemical biophysical cues within environment. This information is transmitted the nucleus through various signaling cascades, culminating in activation or repression of target genes. Transcription factors (TFs) are key mediators these signals, binding specific regulatory elements chromatin. While live-cell imaging has conclusively proven that TF-chromatin interactions highly dynamic, how such transient can have long-term impacts on developmental trajectories disease progression still largely unclear. In this review, we summarize our current understanding dynamic nature TF functions, starting with a historical overview early experiments. We highlight govern dynamics dynamics, turn, affect downstream transcriptional bursting. Finally, conclude open challenges emerging technologies will further regulation.

Language: Английский

Citations

24

Protein-intrinsic properties and context-dependent effects regulate pioneer factor binding and function DOI
Tyler J. Gibson, Elizabeth D. Larson, Melissa M. Harrison

et al.

Nature Structural & Molecular Biology, Journal Year: 2024, Volume and Issue: 31(3), P. 548 - 558

Published: Feb. 16, 2024

Language: Английский

Citations

13

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

10